                         SEQUENCE LISTING

<110>  INSERM
 
<120>  INTERLEUKIN 15 (IL-15) ANTAGONISTS AND USES THEREOF FOR THE 
       TREATMENT OF AUTOIMMUNE DISEASES AND INFLAMMATORY DISEASES

<130>  BIO12129 JACQUES / MC

<160>  15    

<170>  PatentIn version 3.3

<210>  1
<211>  114
<212>  PRT
<213>  Homo sapiens

<400>  1

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 Asx 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>  2
<211>  337
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-IgG1Fc (Murine)

<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 Asp 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                  


Lys Leu Ile Ile Arg 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 Ser Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser 
        115                 120                 125             


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


Leu Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp 
145                 150                 155                 160 


Pro Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr 
                165                 170                 175     


Ala Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser 
            180                 185                 190         


Val Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu 
        195                 200                 205             


Phe Lys Cys Arg Val Asn Ser Ala Ala Phe Pro Ala Pro Ile Glu Lys 
    210                 215                 220                 


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


Ile Pro Pro Pro Lys Glu Gln Met Ala Lys Asp Lys Val Ser Leu Thr 
                245                 250                 255     


Cys Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln 
            260                 265                 270         


Trp Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met 
        275                 280                 285             


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


Ser Asn Trp Glu Ala Gly Asn Thr Phe Thr Cys Ser Val Leu His Glu 
305                 310                 315                 320 


Gly Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly 
                325                 330                 335     


Lys 
    


<210>  3
<211>  341
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-IgG1Fc (Human)

<400>  3

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 Asp 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                  


Lys Leu Ile Ile Arg 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 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu 
        115                 120                 125             


Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr 
    130                 135                 140                 


Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val 
145                 150                 155                 160 


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


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


Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu 
        195                 200                 205             


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


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


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


Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala 
            260                 265                 270         


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


Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu 
    290                 295                 300                 


Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser 
305                 310                 315                 320 


Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser 
                325                 330                 335     


Leu Ser Pro Gly Lys 
            340     


<210>  4
<211>  337
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15-IgG2Fc (Human)

<400>  4

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 Asp 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                  


Lys Leu Ile Ile Arg 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 Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly 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 Gln Phe Asn Trp Tyr Val Asp Gly Met Glu Val His Asn 
                165                 170                 175     


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


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


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


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


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


Cys Leu 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 Met Leu 
        275                 280                 285             


Asp Ser Asp Gly Ser Phe Phe Leu Tyr 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     


Lys 
    


<210>  5
<211>  32
<212>  DNA
<213>  Artificial

<220>
<223>  primer

<400>  5
ctccttgatg ttcttctcct ccagttcctc ac                                   32


<210>  6
<211>  39
<212>  DNA
<213>  Artificial

<220>
<223>  TTCCTGCAGAGCTTCGTACATATTGTCCAAATGTTCATC

<400>  6
ttcctgcaga gcttcgtaca tattgtccaa atgttcatc                            39


<210>  7
<211>  352
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15- Linker-IgG1Fc

<400>  7

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 Asp 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                  


Lys Leu Ile Ile Arg 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 Ser Gly Cys Lys Pro Cys Ile Cys Thr Val Pro Glu Val Ser Ser 
    130                 135                 140                 


Val Phe Ile Phe Pro Pro Lys Pro Lys Asp Val Leu Thr Ile Thr Leu 
145                 150                 155                 160 


Thr Pro Lys Val Thr Cys Val Val Val Asp Ile Ser Lys Asp Asp Pro 
                165                 170                 175     


Glu Val Gln Phe Ser Trp Phe Val Asp Asp Val Glu Val His Thr Ala 
            180                 185                 190         


Gln Thr Gln Pro Arg Glu Glu Gln Phe Asn Ser Thr Phe Arg Ser Val 
        195                 200                 205             


Ser Glu Leu Pro Ile Met His Gln Asp Trp Leu Asn Gly Lys Glu Phe 
    210                 215                 220                 


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


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


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


Met Ile Thr Asp Phe Phe Pro Glu Asp Ile Thr Val Glu Trp Gln Trp 
        275                 280                 285             


Asn Gly Gln Pro Ala Glu Asn Tyr Lys Asn Thr Gln Pro Ile Met Asp 
    290                 295                 300                 


Thr Asp Gly Ser Tyr Phe Val Tyr Ser Lys Leu Asn Val Gln Lys Ser 
305                 310                 315                 320 


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


Leu His Asn His His Thr Glu Lys Ser Leu Ser His Ser Pro Gly Lys 
            340                 345                 350         


<210>  8
<211>  356
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15- Linker - IgG1Fc

<400>  8

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 Asp 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                  


Lys Leu Ile Ile Arg 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 Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu 
    130                 135                 140                 


Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu 
145                 150                 155                 160 


Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser 
                165                 170                 175     


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


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


Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn 
    210                 215                 220                 


Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro 
225                 230                 235                 240 


Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln 
                245                 250                 255     


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


Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val 
        275                 280                 285             


Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro 
    290                 295                 300                 


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


Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val 
                325                 330                 335     


Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu 
            340                 345                 350         


Ser Pro Gly Lys 
        355     


<210>  9
<211>  352
<212>  PRT
<213>  Artificial

<220>
<223>  IL-15- Linker - IgG2Fc

<400>  9

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 Asp 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                  


Lys Leu Ile Ile Arg 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 Val Glu Cys Pro Pro Cys Pro Ala Pro Pro Val Ala Gly Pro Ser 
    130                 135                 140                 


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


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


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


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


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


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


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


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


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


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


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


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


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


<210>  10
<211>  15
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  10

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


<210>  11
<211>  20
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  11

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


Gly Gly Gly Ser 
            20  


<210>  12
<211>  5
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  12

Gly Gly Gly Gly Ser 
1               5   


<210>  13
<211>  3
<212>  PRT
<213>  Artificial

<220>
<223>  linker

<400>  13

Gly Gly Ser 
1           


<210>  14
<211>  3
<212>  PRT
<213>  Artificial

<220>
<223>  GGG

<400>  14

Gly Gly Gly 
1           


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

<220>
<223>  Linker

<400>  15

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


