Antibodies to Chemokine Alpha-5

Abstract

The present invention relates to a novel CKα-5 protein which is a member of the alpha chemokine family. In particular, isolated nucleic acid molecules are provided encoding the human CKα-5 protein. CKα-5 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. Antibodies and fragments thereof that specifically bind to CKα-5 polypeptides are also disclosed, as are compositions and methods for making such antibodies. The invention further relates to screening methods for identifying agonists and antagonists of CKα-5 activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

1 - 28 . (canceled) 
     
     
         29 . A method of screening for a CKα-5 agonist comprising:
 (a) combining (i) a cell expressing a receptor, wherein the receptor activity is enhanced by CKα-5 polypeptide, (ii) CKα-5 polypeptide, and (iii) a test compound;   (b) assaying a calcium mobilization or a chemotactic activity of the cell expressing the receptor; and   (c) comparing the calcium mobilization or the chemotactic activity of the cell with a standard level of calcium mobilization or a standard level of chemotactic activity,   wherein an increase in calcium mobilization or chemotactic activity compared to the standard level indicates the test compound is an agonist of CKα-5 activity.   
     
     
         30 . A method of screening for a CKα-5 antagonist comprising:
 a) combining (i) a cell expressing a receptor, wherein the receptor activity is enhanced by CKα-5 polypeptide, (ii) CKα-5 polypeptide, and (iii) a test compound;   b) assaying a calcium mobilization or a chemotactic activity of the cell expressing the receptor; and   c) comparing the calcium mobilization or the chemotactic activity of the cell with a standard level of calcium mobilization or a standard level of chemotactic activity,   wherein a decrease in calcium mobilization or chemotactic activity compared to the standard level indicates the test compound is an antagonist of CKα-5 activity.   
     
     
         31 . A method of detecting CKα-5 nucleic acid in a sample comprising:
 (a) contacting the sample with a nucleic acid probe under nucleic acid hybridization conditions, wherein the nucleic acid probe comprises SEQ ID NO: 1 or a fragment thereof, a complement of SEQ ID NO: 1 or a fragment thereof, and wherein the fragment comprises at least 20 contiguous nucleic acids; and   (b) detecting hybridization of the probe and the CKα-5 nucleic acid.   
     
     
         32 . The method of  claim 31 , further comprising amplifying the CKα-5 nucleic acid prior to the contacting and detecting steps. 
     
     
         33 . The method of  claim 31 , wherein the fragment comprises at least 20 continuous nucleic acids of nucleic acid residues 622-1303 of SEQ ID NO: 1. 
     
     
         34 . The method of  claim 31 , wherein the fragment comprises at least 20 contiguous nucleic acid residues complementary to nucleic acid residues of 622-1303 of SEQ ID NO: 1. 
     
     
         35 . A method of assaying an expression level of CKα-5 nucleic acid in a biological sample comprising:
 (a) contacting the sample with a hybridization probe under nucleic acid hybridization conditions, wherein the hybridization probe comprises SEQ ID NO: 1 or a fragment thereof, a complement of SEQ ID NO: 1 or a fragment thereof, and wherein the fragment comprises at least 20 contiguous nucleic acids;   (b) detecting a level of hybridization probes, wherein the level of hybridization probes corresponds to the hybridization probes that are hybridized to the CKα-5 nucleic acid; and   (c) comparing the level of hybridization probes with a standard level of hybridization probes.   
     
     
         36 . The method of  claim 35 , wherein the biological sample is selected from the group consisting of: serum, plasma, urine, synovial fluid, spinal fluid, immune tissue, and skeletal tissue. 
     
     
         37 . The method of  claim 35 , wherein the CKα-5 nucleic acid comprises mRNA. 
     
     
         38 . The method of  claim 35 , further comprising amplification of CKα-5 nucleic acid prior to the contacting, detecting and comparing steps. 
     
     
         39 . A method of treating an individual in need of CKα-5 polypeptide activity comprising administering to the individual a therapeutically effective amount of an agonist of CKα-5. 
     
     
         40 . A method of treating an individual in need of CKα-5 polypeptide activity comprising administering to the individual a therapeutically effective amount of a polypeptide selected from the group consisting of SEQ ID NO: 2, a fragment comprising amino acid residues 28-254 of SEQ ID NO: 2, a fragment comprising amino acid residues 28-205 of SEQ ID NO: 2, and a combination thereof. 
     
     
         41 . A method of treating an individual in need of a decreased level of CKα-5 polypeptide activity comprising administering to the individual a therapeutically effective amount of an antagonist of CKα-5. 
     
     
         42 . The method of  claim 41 , wherein the antagonist comprises an isolated antibody or fragment thereof that specifically binds to a protein selected from the group consisting of:
 (a) a protein whose amino acid sequence consists of amino acid residues 1 to 254 of SEQ ID NO: 2;   (b) a protein whose amino acid sequence consists of amino acid residues 28 to 254 of SEQ ID NO: 2;   (c) a protein whose amino acid sequence consists of amino acid residues 28 to 205 of SEQ ID NO: 2;   (d) a protein whose amino acid sequence consists of a portion of SEQ ID NO: 2, wherein said portion is at least 30 contiguous amino acid residues in length; and   (e) a protein whose amino acid sequence consists of a portion of SEQ ID NO: 2, wherein said portion is at least 50 contiguous amino acid residues in length.   
     
     
         43 . The method of  claim 41 , wherein the antagonist comprises antisense RNA.