Human cytokine receptor

Abstract

Cytokines and their receptors have proven usefulness in both basic research and as therapeutics. The present invention provides a new human cytokine receptor designated as “Zcytor16.”

I claim:  
     
         1 . An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: 
 (a) amino acid residues 28 to 127;    (b) amino acid residues 132 to 231;    (c) amino acid residues 28 to 231;    (d) amino acid residues 23 to 230;    (e) amino acid residues 23 to 231; and    (f) amino acid residues 22 to 230;.    
     
     
         2 . The isolated polypeptide of  claim 1 , wherein the polypeptide consists of an amino acid sequence selected from the group consisting of: 
 (a) amino acid residues 28 to 127;    (b) amino acid residues 132 to 231;    (c) amino acid residues 28 to 231;    (d) armino acid residues 23 to 230;    (e) amino acid residues 23 to 231; and    (f) amino acid residues 22 to 230.    
     
     
         3 . The isolated polypeptide of  claim 1 , wherein the isolated polypeptide comprises either amino acid residues amino acid residues 28 to 231 of SEQ ID NO:2.  
     
     
         4 . An isolated nucleic acid molecule, wherein the nucleic acid molecule is either (a) a nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO:3, or (b) a nucleic acid molecule that remains hybridized following stringent wash conditions to a nucleic acid molecule consisting of the nucleotide sequence of nucleotides 64, 67, 82, or 94 to 693 of SEQ ID NO:1, or the complement of the nucleotide sequence of nucleotides 64, 67, 82, or 94 to 693 of SEQ ID NO: 1; or (c) SEQ ID NO: 1 or SEQ ID NO:37, or the complement of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO:37.  
     
     
         5 . The isolated nucleic acid molecule of  claim 4 , wherein any difference between the amino acid sequence encoded by the nucleic acid molecule and the corresponding amino acid sequence of SEQ ID NO:3 is due to a conservative amino acid substitution.  
     
     
         6 . The isolated nucleic acid molecule of  claim 4 , comprising the nucleotide sequence of nucleotides 64 to 693, or 82 to 693 of SEQ ID NO: 1.  
     
     
         7 . A vector, comprising the isolated nucleic acid molecule of  claim 6 .  
     
     
         8 . An expression vector, comprising the isolated nucleic acid molecule of  claim 6 , a transcription promoter, and a transcription terminator, wherein the promoter is operably linked with the nucleic acid molecule, and wherein the nucleic acid molecule is operably linked with the transcription terminator.  
     
     
         9 . A recombinant host cell comprising the expression vector of  claim 8 , wherein the host cell is selected from the group consisting of bacterium, yeast cell, fungal cell, insect cell, mammalian cell, and plant cell.  
     
     
         10 . A method of producing a protein, the method comprising culturing recombinant host cells that comprise the expression vector of  claim 8 , and that produce the protein.  
     
     
         11 . The method of  claim 10 , further comprising isolating the protein from the cultured recombinant host cells.  
     
     
         12 . An antibody or antibody fragment that specifically binds with the polypeptide of  claim 2 .  
     
     
         13 . The antibody of  claim 12 , wherein the antibody is selected from the group consisting of: (a) polyclonal antibody, (b) murine monoclonal antibody, (c) humanized antibody derived from (b), (d) an antibody fragment, and (e) human monoclonal antibody.  
     
     
         14 . An anti-idiotype antibody that specifically binds with the antibody of  claim 12 .  
     
     
         15 . A fusion protein, comprising the polypeptide of  claim 2 .  
     
     
         16 . The fusion protein of  claim 15 , wherein the fusion protein further comprises an immunoglobulin moiety.  
     
     
         17 . An isolated polynucleotide that encodes a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:2 from amino acid 28 to 231, wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide forms a homodimeric, heterodimeric or multimeric receptor complex; and wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide sequence binds IL-TIF or antagonizes IL-TIF activity.  
     
     
         18 . An Isolated polynucleotide according to  claim 17 , wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide further comprises a soluble Class I or Class II cytokine receptor.  
     
     
         19 . An isolated polynucleotide according to  claim 17 , wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide forms a heterodimeric or multimeric receptor complex further comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35), a soluble IL-10 receptor polypeptide (SEQ ID NO:36), or soluble zcytor11receptor polypeptide (SEQ ID NO:34).  
     
     
         20 . An isolated polynucleotide according to  claim 17 , wherein the soluble cytokine receptor polypeptide further encodes an intracellular domain.  
     
     
         21 . An isolated polynucleotide according to  claim 17 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag.  
     
     
         22 . An expression vector comprising the following operably linked elements: 
 (a) a transcription promoter; a first DNA segment encoding a soluble cytokine receptor polypeptide having an amino acid sequence as shown in SEQ ID NO:2 from amino acid 28 to 231; and a transcription terminator; and    (b) a second transcription promoter; a second DNA segment encoding a soluble Class I or Class II cytokine receptor polypeptide; 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.    
     
     
         23 . An expression vector according to  claim 22 , further comprising a secretory signal sequence operably linked to the first and second DNA segments.  
     
     
         24 . An expression vector according to  claim 22 , wherein the second DNA segment encodes a polypeptide comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35), a soluble IL-10 receptor polypeptide (SEQ ID NO:36), or soluble zcytor11 receptor polypeptide (SEQ ID NO:34).  
     
     
         25 . A cultured cell comprising an expression vector according to  claim 22 , wherein the cell expresses the polypeptides encoded by the DNA segments.  
     
     
         26 . A cultured cell comprising an expression vector according to  claim 22 , 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.  
     
     
         27 . A cultured cell into which has been introduced an expression vector according to  claim 22 , wherein the cell expresses a heterodimeric or multimeric soluble receptor polypeptide encoded by the DNA segments.  
     
     
         28 . A cell according to  claim 25 , wherein the cell secretes a soluble cytokine receptor polypeptide heterodimer or multimeric complex.  
     
     
         29 . A cell according to  claim 25 , wherein the cell secretes a soluble cytokine receptor polypeptide heterodimer or multimeric complex that binds IL-TIF or antagonizes IL-TIF activity.  
     
     
         30 . A DNA construct encoding a fusion protein comprising: 
 a first DNA segment encoding a polypeptide having a sequence of amino acid residues as shown in SEQ ID NO:2 from amino acid 28 to 231; and    at least one other DNA segment encoding a soluble Class I or Class II cytokine receptor polypeptide,    wherein the first and other DNA segments are connected in-frame; and    wherein the first and other DNA segments encode the fusion protein.    
     
     
         31 . A DNA construct encoding a fusion protein according to  claim 30 , wherein at least one other DNA segment encodes a polypeptide comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35), a soluble IL-10 receptor polypeptide (SEQ ID NO:36), or soluble zcytor11 receptor polypeptide (SEQ ID NO:34).  
     
     
         32 . An expression vector comprising the following operably linked elements: 
 a transcription promoter;    a DNA construct encoding a fusion protein according to  claim 30;  and    a transcription terminator,    wherein the promoter is operably linked to the DNA construct, and the DNA construct is operably linked to the transcription terminator.    
     
     
         33 . A cultured cell comprising an expression vector according to  claim 32 , wherein the cell expresses a polypeptide encoded by the DNA construct.  
     
     
         34 . A method of producing a fusion protein comprising: 
 culturing a cell according to  claim 33;  and    isolating the polypeptide produced by the cell.    
     
     
         35 . An isolated soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:2 from amino acid 28 to 231, wherein the soluble cytokine receptor polypeptide forms a homodimeric, heterodimeric or multimeric receptor complex; and wherein the soluble cytokine receptor polypeptide encoded by the polynucleotide sequence binds IL-TIF or antagonizes IL-TIF activity.  
     
     
         36 . An isolated polypeptide according to  claim 35 , wherein the soluble cytokine receptor polypeptide forms a heterodimeric or multimeric receptor complex further comprising a soluble Class I or Class II cytokine receptor.  
     
     
         37 . An isolated polypeptide according to  claim 35 , wherein the soluble cytokine receptor polypeptide forms a heterodimeric or multimeric receptor complex comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35), a soluble IL-10 receptor polypeptide (SEQ ID NO:36), or soluble zcytor11 receptor polypeptide (SEQ ID NO:34).  
     
     
         38 . An isolated polypeptide according to  claim 35 , wherein the soluble cytokine receptor polypeptide further comprises an affinity tag, chemical moiety, toxin, or label.  
     
     
         39 . An isolated heterodimeric or multimeric soluble receptor complex comprising soluble receptor subunits, wherein at least one of the soluble receptor subunits comprises a soluble cytokine receptor polypeptide comprising a sequence of amino acid residues as shown in SEQ ID NO:2 from amino acid 28 to 231.  
     
     
         40 . An isolated heterodimeric or multimeric soluble receptor complex according to  claim 39 , further comprising a soluble Class I or Class II cytokine receptor polypeptide.  
     
     
         41 . An isolated heterodimeric or multimeric soluble receptor complex according to  claim 39 , further comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35), a soluble IL-10 receptor polypeptide (SEQ I) NO:36), or soluble zcytor11 receptor polypeptide (SEQ ID NO:34).  
     
     
         42 . A method of producing a soluble cytokine receptor polypeptide that form a heterodimeric or multimeric complex comprising: 
 culturing a cell according to  claim 25;  and    isolating the soluble receptor polypeptides produced by the cell.    
     
     
         43 . A method of producing an antibody to soluble cytokine receptor polypeptide comprising: 
 inoculating an animal with a soluble cytokine receptor polypeptide selected from the group consisting of: 
 (a) a polypeptide comprising a monomeric or homodimeric soluble cytokine receptor comprising a polypeptide as shown in SEQ ID NO:2 from amino acid 28 to 231;  
 (b) a polypeptide of (a) further comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble Class I or Class II cytokine receptor polypeptide;  
 (c) a polypeptide of (a) further comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble CRF2-4 receptor polypeptide (SEQ ID NO:35);  
 (d) a polypeptide of (a) further comprising a soluble cytokine receptor heterodimeric or multimeric receptor complex comprising a soluble IL-10 receptor polypeptide (SEQ ID NO:36); and  
 wherein the polypeptide elicits an immune response in the animal to produce the antibody; and  
   isolating the antibody from the animal.    
     
     
         44 . An antibody produced by the method of  claim 43 , which specifically binds to a homodimeric, heterodimeric or multimeric receptor complex comprising a polypeptide as shown in SEQ ID NO:2 from amino acid 28 to 231.  
     
     
         45 . The antibody of  claim 44 , wherein the antibody is a monoclonal antibody.  
     
     
         46 . An antibody which specifically binds to a homodimeric, heterodimeric or multimeric receptor complex according to  claim 39 .  
     
     
         47 . A method for inhibiting IL-TIF-induced proliferation or differentiation of hematopoietic cells and hematopoietic cell progenitors comprising culturing bone marrow or peripheral blood cells with a composition comprising an amount of soluble cytokine receptor polypeptide as shown in SEQ ID NO:2 from amino acid 28 to 231, sufficient to reduce proliferation or differentiation of the hematopoietic cells in the bone marrow or peripheral blood cells as compared to bone marrow or peripheral blood cells cultured in the absence of soluble cytokine receptor.  
     
     
         48 . The method of  claim 47 , wherein the hematopoietic cells and hematopoietic progenitor cells are lymphoid cells.  
     
     
         49 . The method of  claim 48 , wherein the lymphoid cells are macrophages or T cells.  
     
     
         50 . A method of reducing IL-TIF-induced or IL-9 induced inflammation comprising administering to a mammal with inflammation an amount of a composition of a polypeptide as shown in SEQ ID NO:2 from amino acid 28 to 231 sufficient to reduce inflammation.  
     
     
         51 . A method of suppressing an inflammatory response in a mammal with inflammation comprising: 
 (1) determining a level of serum amyloid A protein;    (2) administering a composition comprising a soluble cytokine receptor polypeptide according to  claim 35  in an acceptable pharmaceutical vehicle;    (3) determining a post administration level of serum amyloid A protein;    (4) comparing the level of serum amyloid A protein in step (1) to the level of serum amyloid A protein in step (3), wherein a lack of increase or a decrease in serum amyloid A protein level is indicative of suppressing an inflammatory response.    
     
     
         52 . A method for detecting a cancer in a patient, comprising: 
 obtaining a tissue or biological sample from a patient;    incubating the tissue or biological sample with an antibody of  claim 12  under conditions wherein the antibody binds to its complementary polypeptide in the tissue or biological sample;    visualizing the antibody bound in the tissue or biological sample; and    comparing levels of antibody bound in the tissue or biological sample from the patient to a normal control tissue or biological sample,    wherein an increase in the level of antibody bound to the patient tissue or biological sample relative to the normal control tissue or biological sample is indicative of a cancer in the patient.    
     
     
         53 . A method of treating a mammal afflicted with an inflammatory disease in which IL-TIF or serum amyloid A plays a role, comprising: 
 administering an antagonist of IL-TIF or serum amyloid A to the mammal such that the inflammation is reduced, wherein the antagonist is selected from the group consisting of: 
 (a) a polypeptide or cytokine binding domain fragment of SEQ ID NO:2;  
 (b) a soluble receptor comprising a polypeptide or cytokine binding domain fragment of SEQ ID NO:34;  
 (c) an antibody that specifically binds a polypeptide or cytokine binding domain fragment of SEQ ID NO:2; and  
 (d) an antibody or binding polypeptide that specifically binds a polypeptide or polypeptide fragment of IL-TIF (SEQ ID NO:15).  
   
     
     
         54 . A method of  claim 53 , wherein the disease is a chronic inflammatory disease.  
     
     
         55 . A method of  claim 54 , wherein the disease is a chronic inflammatory disease selected from the group consisting of: 
 (a) inflammatory bowel disease;    (b) ulcerative colitis;    (c) Crohn's disease;    (d) arthritis; and    (e) psoriasis.    
     
     
         56 . A method of  claim 53 , wherein the disease is an acute inflammatory disease.  
     
     
         57 . A method of  claim 56 , wherein the disease is an acute inflammatory disease selected from the group consisting of: 
 (a) endotoxemia;    (b) septicemia;    (c) toxic shock syndrome; and    (d) infectious disease.    
     
     
         58 . A method of  claim 53 , wherein the antagonist soluble receptor comprising a polypeptide or cytokine binding domain fragment of zcytor11 (SEQ ID NO:34) further comprises a polypeptide or cytokine binding domain fragment of CRF2-4 (SEQ ID NO:35).