Method of identifying agonist and antagonists for tumor necrosis related receptors TR1 and TR2

Abstract

The present invention relates to tumor necrosis factor receptor (TNF-R) related polypeptides and their ligands, hereinafter referred to as TR1, TR2, TL2 and TL4. The invention relates to methods to identify agonists and antagonists of TR1, TR2, TL2 and TL4.

What is claimed is:  
     
         1 . A method for identifying agonists or antagonists to TR1 or TR2 comprising: 
 (a) contacting a candidate compound with TR1 or TR2 in the presence of labeled or unlabeled ligand TL2 or TL4 respectively; and    (b) assessing the ability of said candidate compound to compete with TL2 or TL4 binding to TR1 or TR2 respectively.    
     
     
         2 . The method of  claim 1  in which TR1 or TR2 is on the surface of a host cell, on a cell membrane or on a solid support.  
     
     
         3 . The method of  claim 2  for identifying agonists which further includes determining whether the candidate compound affects a signal generated by TR1 or TR2 polypeptide at the surface of the cell, wherein a candidate compound which increases production of said signal is identified as an agonist.  
     
     
         4 . An agonist identified by the method of  claim 1 ,  2  or  3 .  
     
     
         5 . The method of  claim 2  for identifying antagonists which further includes determining whether the candidate compound affects a signal generated by TR1 or TR2 polypeptide at the surface of the cell, wherein a candidate compound which diminishes production of said signal is identified as an antagonist.  
     
     
         6 . An antagonist identified by the method of  claim 1 ,  2 , or  5 .  
     
     
         7 . A method for identifying agonists or antagonists to TL2 or TL4 comprising: 
 (a) contacting a candidate compound with TL2 or TL4 in the presence of labeled or unlabeled TR1 or TR2 respectively; and    (b) assessing the ability of said candidate compound to compete with TR1 or TR2 binding to TL2 or TL4 respectively.    
     
     
         8 . The method of  claim 7  in which TL2 or TL4 is on the surface of a host cell, on a cell membrane or on a solid support.  
     
     
         9 . The method of  claim 8  for identifying agonists which further includes determining whether the candidate compound affects a signal generated by TL2 or TL4 polypeptide at the surface of the cell, wherein a candidate compound which increases production of said signal is identified as an agonist.  
     
     
         10 . An agonist identified by the method of  claim 9 .  
     
     
         11 . The method of  claim 8  for identifying antagonists which further includes determining whether the candidate compound affects a signal generated by TL2 or TL4 polypeptide at the surface of the cell, wherein a candidate compound which diminishes production of said signal is identified as an antagonist.  
     
     
         12 . An antagonist identified by the method of claim  11 .