Cytokine receptor

Abstract

Novel methods are disclosed for forming a heterodimeric receptor complex with IL-28R and CRF2-4. The methods may be used for detecting and treating viral infections in in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo. The present invention also includes methods for producing the protein, uses therefor and antibodies thereto.

What is claimed is:  
     
         1 . An isolated polynucleotide that encodes a soluble receptor polypeptide comprising a sequence of amino acid residues that is at least 90% identical to the amino acid sequence as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 211, or as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 211.  
     
     
         2 . The polynucleotide of  claim 1 , wherein the soluble receptor polypeptide encoded by the polynucleotide sequence binds a ligand comprising a polypeptide selected from the group consisting of SEQ ID NO:52; SEQ ID NO:55; SEQ ID NO:60; and SEQ ID NO:62.  
     
     
         3 . The isolated polynucleotide according to  claim 1 , wherein the soluble receptor polypeptide encoded by the polynucleotide forms a heterodimeric receptor complex with the subunit as shown in SEQ ID NO: 64.  
     
     
         4 . An isolated polynucleotide that encodes a soluble receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 211, or as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 211.  
     
     
         5 . The polynucleotide of  claim 4 , wherein the soluble receptor polypeptide encoded by the polynucleotide sequence binds a ligand comprising a polypeptide selected from the grouup consisting of of SEQ ID NO:52; SEQ ID NO:55; SEQ ID NO:60; and SEQ ID NO:62.  
     
     
         6 . The isolated polynucleotide according to  claim 4 , wherein the soluble receptor polypeptide encoded by the polynucleotide forms a heterodimeric receptor complex with the subunit as shown in SEQ ID NO: 64.  
     
     
         7 . The isolated polynucleotide according to  claim 4 , wherein the soluble receptor polypeptide further comprises an affinity tag.  
     
     
         8 . An expression vector comprising the following operably linked elements: 
 (a) a transcription promoter; a first DNA segment encoding the soluble receptor polypeptide of  claim 4;  and a transcription terminator; and    (b) a second transcription promoter; a second DNA segment encoding a soluble CRF2-4 polypeptide as shown in SEQ ID NO:64; and a transcription terminator; and    wherein the first and second DNA segments are contained within a single expression vector or are contained within independent expression vectors.    
     
     
         9 . The expression vector according to  claim 8 , further comprising a secretory signal sequence operably linked to the first and second DNA segments.  
     
     
         10 . A cultured cell comprising the expression vector according to  claim 9 , wherein the cell expresses the polypeptides encoded by the DNA segments.  
     
     
         11 . A cultured cell comprising the expression vector according to  claim 9 , wherein the first and second DNA segments are located on independent expression vectors and are co-transfected into the cell, and cell expresses the polypeptides encoded by the DNA segments.  
     
     
         12 . An isolated polypeptide comprising a sequence of amino acid residues that is at least 90% identical to the amino acid sequence as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 163, as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 211, or as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 211.  
     
     
         13 . The polypeptide of  claim 12 , wherein the polypeptide specifically binds a ligand comprising a polypeptide selected from the grouup consisting of SEQ ID NO:52; SEQ ID NO:55; SEQ ID NO:60; and SEQ ID NO:62.  
     
     
         14 . The isolated polypeptide according to  claim 12 , wherein the polypeptide forms a heterodimeric receptor complex with the subunit as shown in SEQ ID NO: 64.  
     
     
         15 . An isolated polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:21 from amino acid residue 21 to amino acid residue 163 or as shown in SEQ ID NO:21 from amino acid residue 1 to amino acid residue 163.  
     
     
         16 . The polypeptide of  claim 15 , wherein the polypeptide specifically binds a ligand comprising a polypeptide selected from the grouup consisting of SEQ ID NO:52; SEQ ID NO:55; SEQ ID NO:60; and SEQ ID NO:62.  
     
     
         17 . An isolated polypeptide according to  claim 15 , wherein the polypeptide forms a heterodimeric receptor complex with the subunit as shown in SEQ ID NO: 64.  
     
     
         18 . An isolated polypeptide according to  claim 15 , wherein the polypeptide further comprises an affinity tag.  
     
     
         19 . A method of producing polypeptides that form a heterodimeric comprising: 
 culturing a cell according to  claim 11;  and    isolating the polypeptides produced by the cell.    
     
     
         20 . A method of producing an antibody to a polypeptide comprising: 
 inoculating an animal with the polypeptide of  claim 15 , wherein the polypeptide elicits an immune response in the animal to produce the antibody; and    isolating the antibody from the animal.    
     
     
         21 . An antibody produced by the method of  claim 20 , which specifically binds to a heterodimeric receptor complex of  claim 17 .  
     
     
         22 . The antibody of  claim 20 , wherein the antibody is a monoclonal antibody.