Cytokine receptor zcytor17 multimers

Abstract

Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytor17-containing multimeric or heterodimer cytokine receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. The present invention also includes methods for producing the multimeric or heterodimeric cytokine receptor, uses therefor and antibodies thereto.

1 . An isolated heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide the amino acid sequence of which has at least 95% sequence identity with amino acid residues 20-732 of SEQ ID NO:111, and a second receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7, and wherein the heterodimeric or multimeric receptor polypeptide binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2. 
     
     
         2 . The isolated heterodimeric or multimeric receptor polypeptide of  claim 1  wherein the receptor polypeptide comprises amino acid residues 20-732 of SEQ ID NO:111. 
     
     
         3 . The isolated heterodimeric or multimeric receptor polypeptide of  claim 1  wherein the second receptor polypeptide comprises amino acid residues 28-979 of SEQ ID NO:7. 
     
     
         4 . An isolated soluble heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide the amino acid sequence of which has at least 95% sequence identity with amino acid residues 20-519 of SEQ ID NO:1, and a second receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7, and wherein the soluble heterodimeric or multimeric receptor binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2. 
     
     
         5 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 4  wherein the receptor polypeptide comprises amino acid residues 20-519 of SEQ ID NO:111. 
     
     
         6 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 4  wherein the soluble heterodimeric or multimeric receptor comprises an immunoglobulin heavy chain constant region. 
     
     
         7 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 6  wherein the immunoglobulin heavy chain constant region is an F c  fragment. 
     
     
         8 . A composition comprising:
 a soluble heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide the amino acid sequence of which has at least 95% sequence identity with amino acid residues 20-519 of SEQ ID NO:111, and a second soluble receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7; and   a pharmaceutically acceptable vehicle.   
     
     
         9 . The composition of  claim 8  wherein the soluble heterodimeric or multimeric receptor polypeptide is fused to an immunoglobulin heavy chain constant region. 
     
     
         10 . The composition of  claim 9  wherein the immunoglobulin heavy chain constant region is an F c  fragment. 
     
     
         11 . An isolated heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide comprising amino acid residues 20-732 of SEQ ID NO:111, and a second receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7. 
     
     
         12 . The isolated heterodimeric or multimeric receptor polypeptide of  claim 11  wherein the receptor polypeptide comprises amino acid residues 1-732 of SEQ ID NO:111. 
     
     
         13 . The isolated heterodimeric or multimeric receptor polypeptide of  claim 11  wherein the second receptor polypeptide comprises amino acid residues 1-979 of SEQ ID NO:7. 
     
     
         14 . An isolated soluble heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide comprising amino acid residues 20-519 of SEQ ID NO:111, and a second soluble receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7. 
     
     
         15 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 14  wherein the soluble heterodimeric or multimeric receptor polypeptide antagonizes an activity of the ligand comprising amino acid residues 27-164 of SEQ ID NO:2. 
     
     
         16 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 14  wherein the soluble multimeric or heterodimeric receptor inhibits proliferation of CD4+ cells, inhibits proliferation of CD19+ cells, inhibits proliferation of inflammatory cells, or inhibits an inflammatory response. 
     
     
         17 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 14  wherein the soluble multimeric or heterodimeric receptor comprises an immunoglobulin heavy chain constant region. 
     
     
         18 . The isolated soluble heterodimeric or multimeric receptor polypeptide of  claim 17  wherein the immunoglobulin heavy chain constant region is an Fc fragment. 
     
     
         19 . A composition comprising:
 a soluble heterodimeric or multimeric receptor polypeptide comprising a first receptor polypeptide comprising amino acid residues 20-519 of SEQ ID NO:111, and a second soluble receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7; and   a pharmaceutically acceptable vehicle.   
     
     
         20 . The composition of  claim 19  wherein the soluble heterodimeric or multimeric receptor polypeptide is fused to an immunoglobulin heavy chain constant region. 
     
     
         21 . The composition of  claim 20  wherein the immunoglobulin heavy chain constant region is an Fc fragment.