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 polynucleotide that encodes a cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-732 of SEQ ID NO:111, wherein the cytokine receptor polypeptide forms a multimeric or heterodimeric cytokine receptor with a second cytokine receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7, and wherein the multimeric or heterodimeric cytokine receptor binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.  
     
     
         2 . The isolated polynucleotide of  claim 1  wherein the cytokine receptor polypeptide comprises amino acid residues 20-732 of SEQ ID NO:111.  
     
     
         3 . The isolated polynucleotide of  claim 1  wherein the isolated polynucleotide comprises nucleotides 228-2366 of SEQ ID NO:110.  
     
     
         4 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA segment encoding a cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-732 of SEQ ID NO:111; and    a transcription terminator;    wherein the cytokine receptor polypeptide forms a multimeric or heterodimeric cytokine receptor with a second cytokine receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7, and wherein the multimeric or heterodimeric cytokine receptor binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.    
     
     
         5 . The expression vector of  claim 4  wherein the cytokine receptor polypeptide comprises amino acid residues 20-732 of SEQ ID NO:111.  
     
     
         6 . The expression vector of  claim 4  wherein the DNA segment comprises nucleotides 228-2366 of SEQ ID NO:110.  
     
     
         7 . An expression vector comprising the following operably linked elements: 
 a) a first transcription promoter; a first DNA segment encoding a first cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-732 of SEQ ID NO:111; and a first transcription terminator; and    b) a second transcription promoter; a second DNA segment encoding a second cytokine receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7; and a second transcription terminator;    wherein the first cytokine receptor polypeptide and the second cytokine receptor polypeptide form a multimeric or heterodimeric cytokine receptor; and    wherein the multimeric or heterodimeric cytokine receptor binds to a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.    
     
     
         8 . The expression vector of  claim 7  wherein the cytokine receptor polypeptide comprises amino acid residues 20-732 of SEQ ID NO:111.  
     
     
         9 . The expression vector of  claim 7  wherein the first DNA segment comprises nucleotides 228-2366 of SEQ ID NO:111.  
     
     
         10 . A cultured cell comprising the expression vector of  claim 4 , wherein the cell expresses the cytokine receptor polypeptide encoded by the DNA segment.  
     
     
         11 . A cultured cell comprising the expression vector of  claim 7 , wherein the cell expresses the first cytokine receptor polypeptide and the second cytokine receptor polypeptide encoded by the DNA segments.  
     
     
         12 . A cultured cell comprising: 
 a first expression vector comprising: 
 a) a first transcription promoter;  
 b) a first DNA segment encoding a first cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-732 of SEQ ID NO:111; and  
 c) a first transcription terminator; and  
   a second expression vector comprising: 
 a) a second transcription promoter;  
 b) a second DNA segment encoding a second cytokine receptor polypeptide comprising amino acid residues 28-979 of SEQ ID NO:7; and  
 c) a second transcription terminator;  
   wherein the first cytokine receptor polypeptide and the second cytokine receptor polypeptide form a multimeric or heterodimeric cytokine receptor; and    wherein the multimeric or heterodimeric cytokine receptor binds to a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.    
     
     
         13 . A method of producing an antibody to a soluble multimeric or heterodimeric cytokine receptor comprising a first cytokine receptor polypeptide consisting of an amino acid sequence having at least 95% sequence identity with amino acid residue 20 to amino acid residue 519 of SEQ ID NO:111 and a second cytokine receptor polypeptide consisting of amino acid residues 28-739 of SEQ ID NO:7, the method comprising: 
 inoculating an animal with the soluble multimeric or heterodimeric cytokine receptor, wherein the soluble multimeric or heterodimeric cytokine receptor elicits an immune response in the animal to produce an antibody that specifically binds the soluble multimeric or heterodimeric cytokine receptor; and    isolating the antibody from the animal.    
     
     
         14 . A method of producing a multimeric or heterodimeric cytokine receptor comprising: 
 culturing a cell according to  claim 11;  and    isolating the multimeric or heterodimeric cytokine receptor produced by the cell.    
     
     
         15 . A method of producing a multimeric or heterodimeric cytokine receptor comprising: 
 culturing a cell according to  claim 12;  and    isolating the multimeric or heterodimeric cytokine receptor produced by the cell.    
     
     
         16 . An isolated polynucleotide that encodes a soluble cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-519 of SEQ ID NO:111, wherein the soluble cytokine receptor polypeptide forms a soluble multimeric or heterodimeric cytokine receptor with a second soluble cytokine receptor comprising amino acid residues 28-739 of SEQ ID NO:7, and wherein the soluble multimeric or heterodimeric cytokine receptor binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.  
     
     
         17 . The isolated polynucleotide of  claim 16  wherein the soluble multimeric or heterodimeric cytokine receptor antagonizes an activity of the ligand comprising amino acid residues 27-164 of SEQ ID NO:2.  
     
     
         18 . The isolated polynucleotide of  claim 17  wherein the soluble multimeric or heterodimeric cytokine receptor inhibits proliferation of immune cells, inhibits proliferation of inflammatory cells, or inhibits an inflammatory response.  
     
     
         19 . The isolated polynucleotide of  claim 16  wherein the soluble heterodimeric or multimeric receptor further comprises an immunoglobulin heavy chain constant region.  
     
     
         20 . The isolated polynucleotide of  claim 19  wherein the immunoglobulin heavy chain constant region is an F c  fragment.  
     
     
         21 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA segment encoding a soluble cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-519 of SEQ ID NO:111; and    a transcription terminator;    wherein the cytokine receptor polypeptide forms a soluble multimeric or heterodimeric cytokine receptor with a second soluble cytokine receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7, and wherein the soluble multimeric or heterodimeric cytokine receptor binds a ligand comprising amino acid residues 27-164 of SEQ ID NO:2.    
     
     
         22 . A cultured cell comprising the expression vector of  claim 21  and a second expression vector comprising: 
 a second transcription promoter;    a second DNA segment encoding a second soluble cytokine receptor polypeptide comprising amino acid residues 28-739 of SEQ ID NO:7; and    a second transcription terminator;    wherein the cell expresses the soluble cytokine receptor polypeptide encoded by the DNA segment and the second soluble cytokine receptor polypeptide encoded by the second DNA segment to form a soluble multimeric or heterodimeric cytokine receptor.    
     
     
         23 . A cultured cell comprising the expression vector of  claim 21 , wherein the cell expresses the soluble cytokine receptor polypeptide encoded by the DNA segment.  
     
     
         24 . A method of producing a soluble multimeric or heterodimeric cytokine receptor comprising: 
 culturing a cell according to  claim 23;  and    isolating the soluble multimeric or heterodimeric cytokine receptor produced by the cell.    
     
     
         25 . A composition comprising: 
 an effective amount of a soluble multimeric or heterodimeric cytokine receptor comprising a first soluble cytokine receptor polypeptide comprising an amino acid sequence having at least 95% sequence identity with amino acid residues 20-519 of SEQ ID NO:111 and a second soluble cytokine receptor comprising amino acid residues 28-739 of SEQ ID NO:7; and    a pharmaceutically acceptable vehicle.    
     
     
         26 . The composition of  claim 25  wherein the soluble multimeric or heterodimeric cytokine receptor further comprises an immunoglobulin heavy chain constant region.  
     
     
         27 . The composition of  claim 26  wherein the immunoglobulin heavy chain constant region is an F c  fragment.