Methods and compositions for modulating the activity of the interleukin-35 receptor complex

Abstract

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interleukin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

1 - 59 . (canceled) 
     
     
         60 . A composition comprising:
 (a) an adjuvant,   (b) a first polypeptide sequence comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:3, and   (c) a second polypeptide sequence comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:6.   
     
     
         61 . A method to identify an Interleukin 35 receptor (IL-35R) complex binding agent comprising the steps of:
 (a) contacting an IL-35R complex comprising a first polypeptide sequence comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:3, and a second polypeptide sequence comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:6, or a cell expressing the IL-35R complex with a candidate compound; and   (b) determining whether the IL-35R complex binds to the candidate compound.   
     
     
         62 . The method of  claim 61 , wherein the binding of the candidate compound to the IL-35R complex is detected by a method selected from the group consisting of:
 (a) detection of binding by direct detecting of candidate compound and IL-35R complex binding; and   (b) detection of binding using a competition binding assay.   
     
     
         63 . The method of  claim 61 , wherein the method further comprises determining the effect of the candidate compound on the activity of the IL-35R complex to thereby determine if the candidate compound modulates the activity of the IL-35R complex. 
     
     
         64 . The method of  claim 61 , wherein the candidate compound is an antibody. 
     
     
         65 . An isolated antibody identified by the method of  claim 64 . 
     
     
         66 . A method of producing an antibody that specifically binds to IL-35R complex, comprising administering the composition of  claim 60  to a subject, and isolating the antibody that binds to IL-35R complex. 
     
     
         67 . An isolated antibody produced by the method of  claim 66 . 
     
     
         68 . A method to identify an IL-35 complex binding agent comprising the steps of:
 (a) contacting a cell comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:3, and a second polypeptide sequence comprising the extracellular domain of the polypeptide sequence set forth in SEQ ID NO:6 with a candidate compound; and   (b) determining whether the IL-35R complex binds to the candidate compound.   
     
     
         69 . The method of  claim 68 , wherein the candidate compound is an antibody. 
     
     
         70 . An isolated antibody identified by the method of  claim 69 .