Methods of mhc class ii epitope mapping, detection of autoimmune t cells and antigens, and autoimmune treatment

Abstract

The present invention provides of using multimeric MHC class II/peptide complexes. In one aspect, methods provided for identifying MHC class II-restricted immune epitopes of a predetermined polypeptide antigen. Methods for identifying an immunostimulatory epitope for a predetermined polypeptide antigen are provided. In a related aspect, methods for screening a therapeutic polypeptide agent for an MHC class II epitope are provided. In other aspects, methods for modulating T cells and for determining or monitoring an MHC class II-restricted immune status of a patient are also provided.

1 - 13 . (canceled) 
     
     
         14 . A method for modulating the state of T cells specific to a predetermined polypeptide antigen, comprising:
 contacting a population of T cells with a MHC class II/peptide tetramer comprising four MHC class II molecule/peptide pairs wherein said peptides comprise a fragment of the predetermined polypeptide antigen and are bound to the MHC class II molecules, said tetramer being conjugated to a biologically active modulatory molecule for stimulating the T cells, said contacting being under conditions conducive to and for a time sufficient that said tetramer binds to T cells specific to said predetermined polypeptide antigen, and   modulating the state of T cells in the population specific to said predetermined polypeptide antigen.   
     
     
         15 . The method of  claim 14 , wherein the MHC class II/peptide tetramer confers epitope-specific binding and targeting of the biologically active modulatory molecule to the T cells. 
     
     
         16 . The method of  claim 14 , wherein the modulation of the state of the T cell is apoptosis, anergy, activation, proliferation, or deviation towards alternative cytokine production, as compared with a T cell which does not bind the MHC class II/peptide tetramer conjugated to the biologically active modulatory molecule. 
     
     
         17 . The method of  claim 14 , wherein the biologically active modulatory molecule is an antibody or a cytotoxin. 
     
     
         18 . The method of  claim 17 , wherein the antibody is anti-CD95 antibody, anti-CTLA4 antibody or anti-CD28 antibody. 
     
     
         19 . The method of  claim 14 , wherein the biologically active modulatory molecule is a member of the B7 family or CD95. 
     
     
         20 . The method of  claim 14 , wherein the biologically active modulatory molecule is coupled to substrate. 
     
     
         21 . The method of  claim 20 , wherein the MHC class II/peptide tetramers are bound to anti-MHC class II antibodies coupled to a microbead. 
     
     
         22 . The method of  claim 14 , wherein the T cells are human T cells. 
     
     
         23 . The method of  claim 14 , wherein the contacting is ex vivo. 
     
     
         24 . The method of  claim 14 , wherein the contacting is in vivo in a human subject. 
     
     
         25 . (canceled)