Immunosuppression

Abstract

The present invention relates, in general, to immunosuppression and, in particular, to a method of inducing an immunosuppressive effect. The invention further relates to a method of screening compounds for immunosuppressive activity.

What is claimed is:  
     
         1 . A method of screening a test compound for immunosuppressive activity comprising: 
 i) contacting CaMKIV and a substrate therefor in the presence of said test compound, under conditions such that CaMKIV-dependent phosphorylation of said substrate can be effected, and    ii) determining the level of phosphorylation of said substrate resulting from step (i) and comparing said level with a level of phosphorylation of said substrate obtained in the absence of said test compound, 
 wherein a reduction in the level of phosphorylation of said substrate in the presence of said test compound indicates that said compound has immunosuppressive activity.  
   
     
     
         2 . The method according to  claim 1  wherein said substrate is a peptide substrate.  
     
     
         3 . The method according to  claim 1  wherein said CaMKIV and said substrate are present in a cell free system.  
     
     
         4 . The method according to  claim 1  wherein said CaMKIV and said substrate are present in a cell.  
     
     
         5 . The method according to  claim 1  wherein, in step (i), said CaMKIV and said substrate therefor are contacted with said test compound in the presence of CaMKIV kinase, calmodulin and calcium under conditions such that CaMKIV kinase dependent phosphorylation of CaMKIV can be effected.  
     
     
         6 . The method according to  claim 5  wherein, in step (ii), the level of phosophorylation of CaMKIV is determined and compared with a level of phosphorylation of CaMKIV obtained in the absence of said test compound, 
 wherein a reduction in the level of phosphorylation of said CaMKIV in the presence of said test compound indicates that said compound has immunosuppressive activity.  
 
     
     
         7 . A non-human transgenic animal that comprises cells nullizygous for a CaMKIV locus.  
     
     
         8 . The animal according to  claim 7  wherein said animal is a rodent.  
     
     
         9 . A non-human transgenic animal in which a kinase minus form of CaMKIV is targeted to the thymocytes thereof.  
     
     
         10 . The animal according to  claim 9  wherein said animal is a rodent.