                         SEQUENCE LISTING

<110>  Cugene Inc.
 
<120>  NOVEL INTERLEUKIN-15 (IL-15) FUSION PROTEINS AND USES THEREOF

<130>  CACCG1.0001WO

<160>  65    

<170>  PatentIn version 3.5

<210>  1
<211>  162
<212>  PRT
<213>  Homo sapiens

<400>  1

Met Arg Ile Ser Lys Pro His Leu Arg Ser Ile Ser Ile Gln Cys Tyr 
1               5                   10                  15      


Leu Cys Leu Leu Leu Asn Ser His Phe Leu Thr Glu Ala Gly Ile His 
            20                  25                  30          


Val Phe Ile Leu Gly Cys Phe Ser Ala Gly Leu Pro Lys Thr Glu Ala 
        35                  40                  45              


Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
    50                  55                  60                  


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
65                  70                  75                  80  


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
                85                  90                  95      


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
            100                 105                 110         


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
        115                 120                 125             


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
    130                 135                 140                 


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
145                 150                 155                 160 


Thr Ser 
        


<210>  2
<211>  114
<212>  PRT
<213>  Homo sapiens

<400>  2

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  3
<211>  267
<212>  PRT
<213>  Homo sapiens

<400>  3

Met Ala Pro Arg Arg Ala Arg Gly Cys Arg Thr Leu Gly Leu Pro Ala 
1               5                   10                  15      


Leu Leu Leu Leu Leu Leu Leu Arg Pro Pro Ala Thr Arg Gly Ile Thr 
            20                  25                  30          


Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser 
        35                  40                  45              


Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys 
    50                  55                  60                  


Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala 
65                  70                  75                  80  


Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp 
                85                  90                  95      


Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val Thr Thr 
            100                 105                 110         


Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly Lys Glu 
        115                 120                 125             


Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr Thr Ala 
    130                 135                 140                 


Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro Ser Thr 
145                 150                 155                 160 


Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr Pro Ser 
                165                 170                 175     


Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser His Gln 
            180                 185                 190         


Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr Val Ala Ile 
        195                 200                 205             


Ser Thr Ser Thr Val Leu Leu Cys Gly Leu Ser Ala Val Ser Leu Leu 
    210                 215                 220                 


Ala Cys Tyr Leu Lys Ser Arg Gln Thr Pro Pro Leu Ala Ser Val Glu 
225                 230                 235                 240 


Met Glu Ala Met Glu Ala Leu Pro Val Thr Trp Gly Thr Ser Ser Arg 
                245                 250                 255     


Asp Glu Asp Leu Glu Asn Cys Ser His His Leu 
            260                 265         


<210>  4
<211>  175
<212>  PRT
<213>  Homo sapiens

<400>  4

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Ser Thr Val 
65                  70                  75                  80  


Thr Thr Ala Gly Val Thr Pro Gln Pro Glu Ser Leu Ser Pro Ser Gly 
                85                  90                  95      


Lys Glu Pro Ala Ala Ser Ser Pro Ser Ser Asn Asn Thr Ala Ala Thr 
            100                 105                 110         


Thr Ala Ala Ile Val Pro Gly Ser Gln Leu Met Pro Ser Lys Ser Pro 
        115                 120                 125             


Ser Thr Gly Thr Thr Glu Ile Ser Ser His Glu Ser Ser His Gly Thr 
    130                 135                 140                 


Pro Ser Gln Thr Thr Ala Lys Asn Trp Glu Leu Thr Ala Ser Ala Ser 
145                 150                 155                 160 


His Gln Pro Pro Gly Val Tyr Pro Gln Gly His Ser Asp Thr Thr 
                165                 170                 175 


<210>  5
<211>  77
<212>  PRT
<213>  Homo sapiens

<400>  5

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro 
65                  70                  75          


<210>  6
<211>  226
<212>  PRT
<213>  Homo sapiens

<400>  6

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly 
225     


<210>  7
<211>  226
<212>  PRT
<213>  Artificial

<220>
<223>  Knob-Fc

<400>  7

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly 
225     


<210>  8
<211>  226
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc

<400>  8

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly 
225     


<210>  9
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Peptide Linker Sequence

<400>  9

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro 
1               5                   10                  15  


<210>  10
<211>  10
<212>  PRT
<213>  Artificial

<220>
<223>  Peptide Linker Sequence

<400>  10

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10  


<210>  11
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  Peptide Linker Sequence

<400>  11

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 
1               5                   10                  15  


<210>  12
<211>  1
<212>  PRT
<213>  Artificial

<220>
<223>  Peptide Linker Sequence

<400>  12

Gly 
1   


<210>  13
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc-Linker 1-IL-15 chain

<400>  13

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser 
225                 230                 235                 240 


Pro Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  14
<211>  318
<212>  PRT
<213>  Artificial

<220>
<223>  Knob-Fc-IL-Linker1-IL-15R??-Sushi+ chain

<400>  14

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser 
225                 230                 235                 240 


Pro Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp 
                245                 250                 255     


Val Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser 
            260                 265                 270         


Gly Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu 
        275                 280                 285             


Asn Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys 
    290                 295                 300                 


Ile Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro 
305                 310                 315             


<210>  15
<211>  336
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-Linker 4-Hole-Fc chain

<400>  15

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser Gly Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro 
        115                 120                 125             


Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser 
    130                 135                 140                 


Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp 
145                 150                 155                 160 


Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn 
                165                 170                 175     


Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val 
            180                 185                 190         


Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu 
        195                 200                 205             


Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys 
    210                 215                 220                 


Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr 
225                 230                 235                 240 


Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser 
                245                 250                 255     


Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu 
            260                 265                 270         


Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu 
        275                 280                 285             


Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys 
    290                 295                 300                 


Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu 
305                 310                 315                 320 


Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
                325                 330                 335     


<210>  16
<211>  299
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15R??-Sushi+-Linker 4-Knob-Fc chain

<400>  16

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Gly Cys Pro 
65                  70                  75                  80  


Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe 
                85                  90                  95      


Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val 
            100                 105                 110         


Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe 
        115                 120                 125             


Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro 
    130                 135                 140                 


Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr 
145                 150                 155                 160 


Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val 
                165                 170                 175     


Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala 
            180                 185                 190         


Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg 
        195                 200                 205             


Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly 
    210                 215                 220                 


Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro 
225                 230                 235                 240 


Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser 
                245                 250                 255     


Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln 
            260                 265                 270         


Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His 
        275                 280                 285             


Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295                 


<210>  17
<211>  313
<212>  PRT
<213>  Artificial

<220>
<223>  Knob-Fc-linker 2-IL-15R??-+ chain

<400>  17

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Thr Cys Pro 
225                 230                 235                 240 


Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser Tyr Ser 
                245                 250                 255     


Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys 
            260                 265                 270         


Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala Thr Asn 
        275                 280                 285             


Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp Pro Ala 
    290                 295                 300                 


Leu Val His Gln Arg Pro Ala Pro Pro 
305                 310             


<210>  18
<211>  350
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc-Linker 2-IL-15 chain

<400>  18

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asn Trp Val Asn 
225                 230                 235                 240 


Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile Gln Ser Met His 
                245                 250                 255     


Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His Pro Ser Cys Lys 
            260                 265                 270         


Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln Val Ile Ser Leu 
        275                 280                 285             


Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu Asn Leu Ile Ile 
    290                 295                 300                 


Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val Thr Glu Ser Gly 
305                 310                 315                 320 


Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile Lys Glu Phe Leu 
                325                 330                 335     


Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn Thr Ser 
            340                 345                 350 


<210>  19
<211>  350
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-Linker 3-Hole-Fc chain

<400>  19

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val 
    130                 135                 140                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
145                 150                 155                 160 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                165                 170                 175     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            180                 185                 190         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        195                 200                 205             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    210                 215                 220                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
225                 230                 235                 240 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                245                 250                 255     


Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
            260                 265                 270         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        275                 280                 285             


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
    290                 295                 300                 


Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
305                 310                 315                 320 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                325                 330                 335     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            340                 345                 350 


<210>  20
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Fc-Linker 3-IL-15 chain

<400>  20

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
225                 230                 235                 240 


Ser Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  21
<211>  350
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-Linker 3-Fc chain

<400>  21

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val 
    130                 135                 140                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
145                 150                 155                 160 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                165                 170                 175     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            180                 185                 190         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        195                 200                 205             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    210                 215                 220                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
225                 230                 235                 240 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                245                 250                 255     


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Ala 
            260                 265                 270         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        275                 280                 285             


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
    290                 295                 300                 


Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
305                 310                 315                 320 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                325                 330                 335     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            340                 345                 350 


<210>  22
<211>  313
<212>  PRT
<213>  Artificial

<220>
<223>  Knob-Fc-Linker 2-IL-15R??-Sushi+ chain

<400>  22

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Thr Cys Pro 
225                 230                 235                 240 


Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser Tyr Ser 
                245                 250                 255     


Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys 
            260                 265                 270         


Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala Thr Asn 
        275                 280                 285             


Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp Pro Ala 
    290                 295                 300                 


Leu Val His Gln Arg Pro Ala Pro Pro 
305                 310             


<210>  23
<211>  313
<212>  PRT
<213>  Artificial

<220>
<223>  Fc-Linker 2-IL-15R??-Sushi+ chain

<400>  23

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile Thr Cys Pro 
225                 230                 235                 240 


Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val Lys Ser Tyr Ser 
                245                 250                 255     


Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly Phe Lys Arg Lys 
            260                 265                 270         


Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn Lys Ala Thr Asn 
        275                 280                 285             


Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile Arg Asp Pro Ala 
    290                 295                 300                 


Leu Val His Gln Arg Pro Ala Pro Pro 
305                 310             


<210>  24
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 S58D Variant Polypeptide

<400>  24

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  25
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 T62D Variant Polypeptide

<400>  25

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Asp Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  26
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 V63F Variant Polypeptide

<400>  26

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Phe Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  27
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 I67V Variant Polypeptide

<400>  27

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Val Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  28
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 I68F Variant Polypeptide

<400>  28

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Phe Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  29
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 I68K Variant Polypeptide

<400>  29

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Lys Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  30
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 I68D Variant Polypeptide

<400>  30

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Asp Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  31
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 I68H Variant Polypeptide

<400>  31

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile His Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  32
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108A Variant Polypeptide

<400>  32

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ala Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  33
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108M Variant Polypeptide

<400>  33

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Met Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  34
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108S Variant Polypeptide

<400>  34

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ser Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  35
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108S/D30T Variant Polypeptide

<400>  35

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Thr Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ser Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  36
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108S/V31Y Variant Polypeptide

<400>  36

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Tyr His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ser Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  37
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108S/H32E Variant Polypeptide

<400>  37

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val Glu 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ser Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  38
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Q108S/D30T/V31Y/H32E Variant Polypeptide

<400>  38

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Thr Tyr Glu 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Ser Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


<210>  39
<211>  110
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 deletion 111-114 Variant Polypeptide

<400>  39

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe 
            100                 105                 110 


<210>  40
<211>  108
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 deletion 109-114 Variant Polypeptide

<400>  40

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln 
            100                 105             


<210>  41
<211>  107
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 deletion 108-114 Variant Polypeptide

<400>  41

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val 
            100                 105         


<210>  42
<211>  104
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 deletion 105-114 Variant Polypeptide

<400>  42

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val 
            100                 


<210>  43
<211>  116
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Insertion 'GS' after N95 Variant Polypeptide

<400>  43

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Gly 
                85                  90                  95      


Ser Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe 
            100                 105                 110         


Ile Asn Thr Ser 
        115     


<210>  44
<211>  119
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Insertion 'GGSGG' after N95 Variant Polypeptide

<400>  44

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Gly 
                85                  90                  95      


Gly Ser Gly Gly Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val 
            100                 105                 110         


Gln Met Phe Ile Asn Thr Ser 
        115                 


<210>  45
<211>  123
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 Insertion 'GSSGGSGGS' after N95 Variant Polypeptide

<400>  45

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Gly 
                85                  90                  95      


Ser Ser Gly Ser Ser Gly Gly Ser Ile Lys Glu Phe Leu Gln Ser Phe 
            100                 105                 110         


Val His Ile Val Gln Met Phe Ile Asn Thr Ser 
        115                 120             


<210>  46
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Fc-Linker 3-IL-15 S58D chain

<400>  46

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
225                 230                 235                 240 


Ser Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  47
<211>  9
<212>  PRT
<213>  Artificial

<220>
<223>  Peptide Linker Sequence

<400>  47

Gly Gly Gly Gly Ser Gly Gly Gly Gly 
1               5                   


<210>  48
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc-Linker 3-IL-15 S58D chain

<400>  48

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
225                 230                 235                 240 


Ser Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  49
<211>  350
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 S58D-Linker 3-Hole-Fc chain

<400>  49

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val 
    130                 135                 140                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
145                 150                 155                 160 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                165                 170                 175     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            180                 185                 190         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        195                 200                 205             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    210                 215                 220                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
225                 230                 235                 240 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                245                 250                 255     


Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala 
            260                 265                 270         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        275                 280                 285             


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
    290                 295                 300                 


Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
305                 310                 315                 320 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                325                 330                 335     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            340                 345                 350 


<210>  50
<211>  350
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15 S58D-Linker 3-Fc chain

<400>  50

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
        115                 120                 125             


Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val 
    130                 135                 140                 


Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr 
145                 150                 155                 160 


Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu 
                165                 170                 175     


Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys 
            180                 185                 190         


Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser 
        195                 200                 205             


Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys 
    210                 215                 220                 


Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile 
225                 230                 235                 240 


Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro 
                245                 250                 255     


Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Ala 
            260                 265                 270         


Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn 
        275                 280                 285             


Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser 
    290                 295                 300                 


Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg 
305                 310                 315                 320 


Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu 
                325                 330                 335     


His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly 
            340                 345                 350 


<210>  51
<211>  308
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15R??-Sushi+Linker 2-Knob-Fc chain

<400>  51

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Gly Gly Gly 
65                  70                  75                  80  


Gly Ser Gly Gly Gly Gly Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala 
                85                  90                  95      


Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            100                 105                 110         


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        115                 120                 125             


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
    130                 135                 140                 


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
145                 150                 155                 160 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                165                 170                 175     


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
            180                 185                 190         


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        195                 200                 205             


Gln Val Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln 
    210                 215                 220                 


Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
225                 230                 235                 240 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                245                 250                 255     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            260                 265                 270         


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
        275                 280                 285             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    290                 295                 300                 


Leu Ser Pro Gly 
305             


<210>  52
<211>  308
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15R??-Sushi+Linker 2-Fc chain

<400>  52

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Asp Pro Ala Leu Val His Gln Arg Pro Ala Pro Pro Gly Gly Gly 
65                  70                  75                  80  


Gly Ser Gly Gly Gly Gly Ser Cys Pro Pro Cys Pro Ala Pro Glu Ala 
                85                  90                  95      


Ala Gly Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
            100                 105                 110         


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
        115                 120                 125             


Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val 
    130                 135                 140                 


Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser 
145                 150                 155                 160 


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
                165                 170                 175     


Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala 
            180                 185                 190         


Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro 
        195                 200                 205             


Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln 
    210                 215                 220                 


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
225                 230                 235                 240 


Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr 
                245                 250                 255     


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
            260                 265                 270         


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
        275                 280                 285             


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
    290                 295                 300                 


Leu Ser Pro Gly 
305             


<210>  53
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc-Linker 1-IL-15-S58D chain

<400>  53

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser 
225                 230                 235                 240 


Pro Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Asp Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  54
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Hole-Fc-Linker 3-IL-15 chain

<400>  54

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 
225                 230                 235                 240 


Ser Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  55
<211>  355
<212>  PRT
<213>  Artificial

<220>
<223>  Knob-Fc-Linker 1-IL-15 chain

<400>  55

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly 
1               5                   10                  15      


Ala Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met 
            20                  25                  30          


Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His 
        35                  40                  45              


Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val 
    50                  55                  60                  


His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr 
65                  70                  75                  80  


Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly 
                85                  90                  95      


Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile 
            100                 105                 110         


Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val 
        115                 120                 125             


Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser 
    130                 135                 140                 


Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu 
145                 150                 155                 160 


Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro 
                165                 170                 175     


Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val 
            180                 185                 190         


Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met 
        195                 200                 205             


His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser 
    210                 215                 220                 


Pro Gly Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser 
225                 230                 235                 240 


Pro Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu 
                245                 250                 255     


Ile Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val 
            260                 265                 270         


His Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu 
        275                 280                 285             


Gln Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val 
    290                 295                 300                 


Glu Asn Leu Ile Ile Leu Ala Asn Asn Ser Leu Ser Ser Asn Gly Asn 
305                 310                 315                 320 


Val Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn 
                325                 330                 335     


Ile Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile 
            340                 345                 350         


Asn Thr Ser 
        355 


<210>  56
<211>  1131
<212>  DNA
<213>  Artificial

<220>
<223>  P-0313 Chain 1

<400>  56
atggatatgc gggtgcctgc tcagctgctg ggcctgctgc tgctgtggct gcgaggggct       60

agatgtgata aaactcatac ttgtcctcca tgcccagcac ctgaggcagc aggcgcccca      120

tccgtgttcc tgtttccccc taagcccaag gacacactga tgatctcccg tacgccagag      180

gtgacatgcg tggtggtgga cgtgagccac gaggaccccg aggtgaagtt taactggtac      240

gtggacggcg tggaggtgca caatgccaag acaaagccta gggaggagca gtacaattct      300

acctatcgcg tggtgagcgt gctgacagtg ctgcaccagg attggctgaa cggcaaggag      360

tataagtgca aggtgtccaa taaggccctg cctgccccaa tcgagaagac catctctaag      420

gccaagggcc agcccagaga gcctcaggtg tacacactgc ctccaagcag agacgagctg      480

accaagaacc aggtgtccct gacatgtctg gtgaagggct tctatccctc tgatatcgcc      540

gtggagtggg agagcaatgg ccagcctgag aacaattaca agaccacacc ccctgtgctg      600

gacagcgatg gctccttctt tctgtattcc aagctgaccg tggataagtc tcggtggcag      660

cagggcaacg tgttttcctg ctctgtgatg cacgaagcac tgcataacca ctacacccag      720

aagagcctga gcctgtcccc cgggggaggc ggaggatctg gtggcggagg aagcggaggc      780

ggcggctcca actgggtgaa tgtgatcagc gacctgaaga agatcgagga tctgatccag      840

tccatgcaca tcgacgccac cctgtataca gagtctgatg tgcaccccag ctgcaaggtg      900

accgccatga agtgttttct gctggagctg caggtcatca gcctggagtc cggcgacgca      960

gacatccacg ataccgtgga gaatctgatc atcctggcca acaattccct gtctagcaac     1020

ggcaatgtga cagagtctgg ctgcaaggag tgtgaggagc tggaggagaa gaatatcaaa     1080

gagttcctgc agagtttcgt ccacatcgtc cagatgttta tcaatacctc a              1131


<210>  57
<211>  321
<212>  DNA
<213>  Artificial

<220>
<223>  Chain 2 of fusion proteins P-0313, P-0234, P-0666, and P-0668

<400>  57
atggctccac ggcgggctcg gggctgtcgc accctggggc tgcctgctct gctgctgctg       60

ctgctgctga gaccacctgc tacacgcggc atcacctgcc cacctccaat gagcgtggag      120

cacgcagaca tctgggtgaa gtcttacagc ctgtatagcc gggagagata catctgcaac      180

tccggcttca agcggaaggc cggcaccagc tccctgacag agtgcgtgct gaacaaggcc      240

acaaatgtgg cccactggac cacaccttcc ctgaagtgca tccgggaccc cgccctggtg      300

caccagcgcc cagccccccc t                                                321


<210>  58
<211>  1131
<212>  DNA
<213>  Artificial

<220>
<223>  P-0234 Chain 1

<400>  58
atggatatgc gggtgcctgc tcagctgctg ggcctgctgc tgctgtggct gcgaggggct       60

agatgtgata aaactcatac ttgtcctcca tgcccagcac ctgaggcagc aggcgcccca      120

tccgtgttcc tgtttccccc taagcccaag gacacactga tgatctcccg tacgccagag      180

gtgacatgcg tggtggtgga cgtgagccac gaggaccccg aggtgaagtt taactggtac      240

gtggacggcg tggaggtgca caatgccaag acaaagccta gggaggagca gtacaattct      300

acctatcgcg tggtgagcgt gctgacagtg ctgcaccagg attggctgaa cggcaaggag      360

tataagtgca aggtgtccaa taaggccctg cctgccccaa tcgagaagac catctctaag      420

gccaagggcc agcccagaga gcctcaggtg tacacactgc ctccaagcag agacgagctg      480

accaagaacc aggtgtccct gacatgtctg gtgaagggct tctatccctc tgatatcgcc      540

gtggagtggg agagcaatgg ccagcctgag aacaattaca agaccacacc ccctgtgctg      600

gacagcgatg gctccttctt tctgtattcc aagctgaccg tggataagtc tcggtggcag      660

cagggcaacg tgttttcctg ctctgtgatg cacgaagcac tgcataacca ctacacccag      720

aagagcctga gcctgtcccc cgggggaggc ggaggatctg gtggcggagg aagcggaggc      780

ggcggctcca actgggtgaa tgtgatcagc gacctgaaga agatcgagga tctgatccag      840

tccatgcaca tcgacgccac cctgtataca gagtctgatg tgcaccccag ctgcaaggtg      900

accgccatga agtgttttct gctggagctg caggtcatca gcctggagtc cggcgacgca      960

agcatccacg ataccgtgga gaatctgatc atcctggcca acaattccct gtctagcaac     1020

ggcaatgtga cagagtctgg ctgcaaggag tgtgaggagc tggaggagaa gaatatcaaa     1080

gagttcctgc agagtttcgt ccacatcgtc cagatgttta tcaatacctc a              1131


<210>  59
<211>  1131
<212>  DNA
<213>  Artificial

<220>
<223>  P-0666 Chain 1

<400>  59
atggatatgc gagtgcctgc tcagctgctg ggcctgctgc tgctgtggct gcggggggct       60

agatgcgata aaactcatac ctgtcctcca tgcccagcac ctgaggcagc aggcgcccca      120

tccgtgttcc tgtttccccc taagcccaag gacaccctga tgatctctcg tacgcccgag      180

gtgacatgcg tggtggtgga cgtgagccac gaggaccccg aggtgaagtt caactggtac      240

gtggatggcg tggaggtgca caatgccaag acaaagcctc gggaggagca gtacaactcc      300

acctatagag tggtgtctgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag      360

tacaagtgca aggtgtccaa taaggccctg ccagccccca tcgagaagac catcagcaag      420

gccaagggcc agcctaggga gccacaggtg tataccctgc caccctgccg cgaggagatg      480

acaaagaacc aggtgtccct gtcttgtgcc gtgaagggct tctacccttc tgacatcgcc      540

gtggagtggg agagcaatgg ccagccagag aacaattata agaccacacc tccagtgctg      600

gactctgatg gcagcttctt tctggtgagc aagctgaccg tggataagtc caggtggcag      660

cagggcaacg tgtttagctg ttccgtgatg cacgaggccc tgcacaatca ctacacacag      720

aagtctctga gcctgtcccc cgggggaggc ggaggatctg gtggcggagg aagcggaggc      780

ggcggctcca actgggtgaa tgtgatcagc gacctgaaga agatcgagga tctgatccag      840

tccatgcaca tcgacgccac cctgtataca gagtctgatg tgcaccccag ctgcaaggtg      900

accgccatga agtgttttct gctggagctg caggtcatca gcctggagtc cggcgacgca      960

gacatccacg ataccgtgga gaatctgatc atcctggcca acaattccct gtctagcaac     1020

ggcaatgtga cagagtctgg ctgcaaggag tgtgaggagc tggaggagaa gaatatcaaa     1080

gagttcctgc agagtttcgt ccacatcgtc cagatgttta tcaatacctc a              1131


<210>  60
<211>  744
<212>  DNA
<213>  Artificial

<220>
<223>  P-0666 Chain 3

<400>  60
atggatatgc gggtgcctgc tcagctgctg ggcctgctgc tgctgtggct gcgaggggct       60

agatgtgata aaactcatac ttgtcctcca tgcccagcac ctgaggcagc aggcgcccca      120

tccgtgttcc tgtttccccc taagcccaag gacacactga tgatctcccg tacgccagag      180

gtgacatgcg tggtggtgga cgtgtctcac gaggaccccg aggtgaagtt caactggtac      240

gtggatggcg tggaggtgca caatgccaag accaagccca gggaggagca gtacaacagc      300

acctatcgcg tggtgtccgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag      360

tataagtgca aggtgtccaa taaggccctg ccagccccca tcgagaagac catcagcaag      420

gcaaagggac agcctcggga gccacaggtg tgcaccctgc caccctctag agaggagatg      480

acaaagaacc aggtgagcct gtggtgtctg gtgaagggct tctacccttc cgacatcgcc      540

gtggagtggg agtctaatgg ccagccagag aacaattaca agaccacacc tccagtgctg      600

gactctgatg gcagcttctt tctgtattct aagctgaccg tggataagag caggtggcag      660

cagggcaacg tgttttcctg ctctgtgatg cacgaggccc tgcacaatca ctacacacag      720

aagagcctgt ccctgtctcc cggg                                             744


<210>  61
<211>  1110
<212>  DNA
<213>  Artificial

<220>
<223>  P-0668 Chain 1

<400>  61
atgtatcgga tgcagctgct gtcttgtatc gctctgtcac tggctctggt cactaattct       60

aactgggtca atgtcatttc tgatctgaag aagatcgagg acctgatcca gagcatgcac      120

atcgatgcca ccctgtacac agagtccgac gtgcacccat cttgcaaggt gaccgcaatg      180

aagtgtttcc tgctggagct gcaggtcatc agcctggaga gcggcgacgc agatatccac      240

gataccgtgg agaacctgat catcctggca aacaattccc tgagctccaa cggaaatgtg      300

acagagtctg gatgcaagga gtgtgaggag ctggaggaga agaacatcaa ggagttcctg      360

cagtcttttg tgcacatcgt gcagatgttc atcaatacat ccggcggcgg cggctccggc      420

ggcggcggct ctggcggcgg cggcagctgc cccccttgtc cagcccccga ggccgctggg      480

gcaccaagcg tgttcctgtt ccctccaaaa ccaaaagata ctctgatgat tagccgtacg      540

ccagaggtga catgcgtggt ggtggacgtg agccacgagg accccgaggt gaagtttaac      600

tggtacgtgg acggcgtgga ggtgcacaat gccaagacaa agcctaggga ggagcagtac      660

aattctacct atcgcgtggt gagcgtgctg acagtgctgc accaggattg gctgaacggc      720

aaggagtata agtgcaaggt gtccaataag gccctgcctg ccccaatcga gaagaccatc      780

tctaaggcca agggccagcc cagagagcct caggtgtaca cactgcctcc aagcagagac      840

gagctgacca agaaccaggt gtccctgaca tgtctggtga agggcttcta tccctctgat      900

atcgccgtgg agtgggagag caatggccag cctgagaaca attacaagac cacaccccct      960

gtgctggaca gcgatggctc cttctttctg tattccaagc tgaccgtgga taagtctcgg     1020

tggcagcagg gcaacgtgtt ttcctgctct gtgatgcacg aagcactgca taaccactac     1080

acccagaaga gcctgagcct gtcccccggg                                      1110


<210>  62
<211>  1005
<212>  DNA
<213>  Artificial

<220>
<223>  P-0314 Chain 1

<400>  62
atggatatgc gggtgcctgc tcagctgctg ggcctgctgc tgctgtggct gcgaggggct       60

agatgtgata aaactcatac ttgtcctcca tgcccagcac ctgaggcagc aggcgcccca      120

tccgtgttcc tgtttccccc taagcccaag gacacactga tgatctcccg tacgccagag      180

gtgacatgcg tggtggtgga cgtgagccac gaggaccccg aggtgaagtt taactggtac      240

gtggacggcg tggaggtgca caatgccaag acaaagccta gggaggagca gtacaattct      300

acctatcgcg tggtgagcgt gctgacagtg ctgcaccagg attggctgaa cggcaaggag      360

tataagtgca aggtgtccaa taaggccctg cctgccccaa tcgagaagac catctctaag      420

gccaagggcc agcccagaga gcctcaggtg tacacactgc ctccaagcag agacgagctg      480

accaagaacc aggtgtccct gacatgtctg gtgaagggct tctatccctc tgatatcgcc      540

gtggagtggg agagcaatgg ccagcctgag aacaattaca agaccacacc ccctgtgctg      600

gacagcgatg gctccttctt tctgtattcc aagctgaccg tggataagtc tcggtggcag      660

cagggcaacg tgttttcctg ctctgtgatg cacgaagcac tgcataacca ctacacccag      720

aagagcctga gcctgtcccc cgggggcggc ggcggcagcg gaggcggcgg ctccatcacc      780

tgtccacccc ctatgagcgt ggagcacgcc gatatctggg tgaagagcta ctccctgtat      840

agccgggaga gatatatctg caattccggc tttaagcgca aggccggcac ctctagcctg      900

acagagtgcg tgctgaacaa ggccaccaat gtggcccact ggacaacccc aagcctgaag      960

tgtattagag accctgccct ggtgcatcag cggcctgctc cccca                     1005


<210>  63
<211>  402
<212>  DNA
<213>  Artificial

<220>
<223>  P-0314 Chain 2

<400>  63
atgtaccgga tgcagctgct gtcctgcatc gccctgtctc tggccctggt gaccaactct       60

aattgggtga acgtgatcag cgacctgaag aagatcgagg atctgatcca gtctatgcac      120

atcgacgcca ccctgtatac agagagcgat gtgcacccct cctgcaaggt gacagccatg      180

aagtgtttcc tgctggagct gcaggtcatc agcctggaga gcggcgacgc agacatccac      240

gataccgtgg agaacctgat catcctggcc aataactccc tgagctccaa cggcaatgtg      300

acagagtctg gctgcaagga gtgtgaggag ctggaggaga agaacatcaa ggagttcctg      360

cagagctttg tgcacatcgt gcagatgttt atcaatacct cc                         402


<210>  64
<211>  296
<212>  PRT
<213>  Artificial

<220>
<223>  Benchmark Chain1

<400>  64

Ile Thr Cys Pro Pro Pro Met Ser Val Glu His Ala Asp Ile Trp Val 
1               5                   10                  15      


Lys Ser Tyr Ser Leu Tyr Ser Arg Glu Arg Tyr Ile Cys Asn Ser Gly 
            20                  25                  30          


Phe Lys Arg Lys Ala Gly Thr Ser Ser Leu Thr Glu Cys Val Leu Asn 
        35                  40                  45              


Lys Ala Thr Asn Val Ala His Trp Thr Thr Pro Ser Leu Lys Cys Ile 
    50                  55                  60                  


Arg Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro 
65                  70                  75                  80  


Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys 
                85                  90                  95      


Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val 
            100                 105                 110         


Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr 
        115                 120                 125             


Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu 
    130                 135                 140                 


Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His 
145                 150                 155                 160 


Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys 
                165                 170                 175     


Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln 
            180                 185                 190         


Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu 
        195                 200                 205             


Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro 
    210                 215                 220                 


Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn 
225                 230                 235                 240 


Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu 
                245                 250                 255     


Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val 
            260                 265                 270         


Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 
        275                 280                 285             


Lys Ser Leu Ser Leu Ser Pro Gly 
    290                 295     


<210>  65
<211>  114
<212>  PRT
<213>  Artificial

<220>
<223>  Benchmark Chain 2

<400>  65

Asn Trp Val Asn Val Ile Ser Asp Leu Lys Lys Ile Glu Asp Leu Ile 
1               5                   10                  15      


Gln Ser Met His Ile Asp Ala Thr Leu Tyr Thr Glu Ser Asp Val His 
            20                  25                  30          


Pro Ser Cys Lys Val Thr Ala Met Lys Cys Phe Leu Leu Glu Leu Gln 
        35                  40                  45              


Val Ile Ser Leu Glu Ser Gly Asp Ala Ser Ile His Asp Thr Val Glu 
    50                  55                  60                  


Asn Leu Ile Ile Leu Ala Asn Asp Ser Leu Ser Ser Asn Gly Asn Val 
65                  70                  75                  80  


Thr Glu Ser Gly Cys Lys Glu Cys Glu Glu Leu Glu Glu Lys Asn Ile 
                85                  90                  95      


Lys Glu Phe Leu Gln Ser Phe Val His Ile Val Gln Met Phe Ile Asn 
            100                 105                 110         


Thr Ser 
        


