MHC Class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete.
Selective expansion and activation of a very small number of antigen-specific CD4(+) T cells is a remarkable and essential property of the adaptive immune response. Antigen-specific T cells were until recently identified only indirectly by functional assays, such as antigen-induced cytokine secretion and proliferation. The advent of MHC Class II tetramers has added a pivotal tool to our research armamentarium, allowing the definition of allo- and autoimmune responses in deeper detail. Rare antigen-specific CD4(+) cells can now be selectively identified, isolated and characterized. The same tetramer reagents also provide a new mean of stimulating T cells, more closely reproducing the MHC-peptide/TCR interaction. This property allows the use of tetramers to direct T cells toward the more desirable outcome, that is, activation (in malignancies and infectious diseases) or Th2/T regulatory cell deviation, anergy and deletion (in autoimmune diseases). These experimental approaches hold promise for diagnostic, prognostic and therapeutic applications.
Mallone
Roberto
R
Benaroya Research Institute at Virginia Mason, Seattle, WA 98101, USA. rmallone@benaroyaresearch.org
Nepom
Gerald T
GT
D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry / Q000379:methods*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013194:Staining and Labeling / Q000379:methods
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell