Cytokine polypeptides and nucleic acids

Abstract

New cytokine polypeptides, and nucleic acids encoding them, are provided. Compositions including these polypeptides and nucleic acids, recombinant cells comprising said polypeptides and nucleic acids, methods of making the polypeptides and nucleic acid, antibodies to the polypeptides, and methods of using the polypeptides and nucleic acids are provided. Integrated systems comprising the sequences of the nucleic acids or polypeptides are also provided.

1 . An isolated or recombinant nucleic acid, comprising a polynucleotide sequence selected from the group consisting of: 
 (a) a polynucleotide sequence comprising the mature polypeptide coding region of a sequence selected from SEQ ID NO:1 to SEQ ID NO:7, or a complementary polynucleotide sequence thereof;    (b) a polynucleotide sequence encoding a polypeptide, the polypeptide comprising an amino acid sequence having at least 90% amino acid sequence identity to the mature polypeptide region of a sequence selected from SEQ ID NO:8 to SEQ ID NO:14, or a complementary polynucleotide sequence thereof;    (c) a polynucleotide sequence which hybridizes under highly stringent conditions over substantially the entire length of polynucleotide sequence (a) or (b);    (d) a polynucleotide sequence comprising a fragment of (a), (b), or (c), which fragment encodes a polypeptide having T-cell proliferative activity in the presence of a p35 polypeptide.    
     
     
         2 . The nucleic acid of  claim 1 , wherein the nucleic acid encodes a polypeptide having T-cell proliferative activity in the presence of a p35 polypeptide, the p35 polypeptide comprising a sequence selected from a mature polypeptide region of a wild-type p35 polypeptide and a mature polypeptide region of a modified p35 polypeptide.  
     
     
         3 . The nucleic acid of  claim 2 , wherein the p35 polypeptide comprises a sequence comprising amino acid residues 23 to 219 of SEQ ID NO:36.  
     
     
         4 . The nucleic acid of  claim 3 , wherein the p35 polypeptide comprises a sequence comprising amino acid residues 23 to 219 of SEQ ID NO:31 or SEQ ID NO:32.  
     
     
         5 . An isolated or recombinant nucleic acid, comprising a polynucleotide sequence encoding a modified p40 polypeptide comprising a modification at an equivalent position to that in the amino acid sequence of a human p40 polypeptide (SEQ ID NO:15), the modification selected from the group consisting of: 
 (a) a substitution of the specified amino acid for a different amino acid at one or more equivalent position selected from Leu62, Ser71, Gln78, His99, Thr127, Arg130, Lys185, Glu186, Tyr187, Glu188, Ser190, Asp196, Met211, Val289, Ser305, Ser307, Arg309, and Gln311;    (b) a deletion of equivalent amino acid residues Arg181 to Asn184 inclusive, or a substitution, of equivalent amino acid residues Arg181 to Asn184 inclusive, for the amino acids Ser-(Leu or Met)-(Glu or Asp)-His-Arg;    (c) a deletion of equivalent amino acid residues Asp287 and Arg288; and    (d) at least two of (a), (b), or (c);    wherein the numbering of amino acid residue positions corresponds to that of SEQ ID NO:15.    
     
     
         6 . The nucleic acid of  claim 5 , wherein the modified p40 polypeptide is a modification of a p40 polypeptide selected from the group consisting of p40 polypeptides encoded by nucleic acids having the GenBank accession numbers: M65272, M65290, U19841, U19834, Y11129, U83184, Y07762, AF054607, U49100, AF091134, U57752, U10160, AF007576, AF004024, U11815, U08317, X97019, AF082494, AF133197, U16674, M86671, S82426, AF097507, and AF046211.  
     
     
         7 . The nucleic acid of  claim 5 , wherein the modified p40 polypeptide is a modification of a human p40 polypeptide comprising amino acid residues 23 to 328 of SEQ ID NO:15.  
     
     
         8 . The nucleic acid of  claim 5 , wherein the modified p40 polypeptide comprises one or more substitution selected from the group consisting of: 
 Leu62Ser; Ser71Thr; Gln78His; His99(Arg or Gln); Thr127(Ser or Ile); Arg130Lys; Lys185Glu; Glu186Tyr; Tyr187(Lys or Asn); Glu188Lys; Ser190(Arg or Thr); Asp196Gly; Met211Val; Val289(Ile or Leu); Ser305Lys; Ser307Arg; Arg309Gln; and Gln311Arg.    
     
     
         9 . The nucleic acid of  claim 5 , wherein the encoded polypeptide comprises one or more substitution selected from the group consisting of: 
 Lys27Glu; Asp29Asn; Asp40Asn; Met45Thr; Thr49Ala; Glu67Gly, His91Arg; Glu95(Ala or Thr), Val96Ala; Glu122Lys; Asn125Ala; Asn135Asp; Arg139His; Thr147Ala; Thr153Lys; Ser155Thr; Ser163Thr; Gln166(Arg or His), Ala172Thr; Ala173Val; Thr174Leu; Ala177Glu; Glu178Asp; Arg179Leu; Val180Gly; Ala201Ser; Val212Leu; Asp213Glu; Val215Ile; Ser226Arg; Lys244Arg; Gln251His; Val254Ile; Ser255Asn; Glu257Gly; Thr264(Ala or Ile); Thr272Met; Cys274Gly; Val275Ile; Lys280Arg; Ser281Asn; Lys285Asp; Lys286Arg; Phe290Ser; Thr291(Met or Val); Lys293Gln; Thr297Lys; Ile299(Thr or Val); Arg301His; Asn303Asp; Ser318Phe; Glu321Asp; Pro326Ser; Cys327Leu; and Ser328(Gly or Gln).    
     
     
         10 . The nucleic acid of  claim 5 , wherein the encoded polypeptide has T-cell proliferative activity in the presence of a p35 polypeptide.  
     
     
         11 - 183 . (canceled)