ANTIGEN ANALOGS MHC COMPLEXES AS SPECIFIC T-CELL RECEPTOR ANTAGONISTS

Recent studies demonstrated that antigen analogs can act as powerful a nd specific inhibitors of T cell activation, leading to the formulatio n of the concept that antigen analog/MHC complexes may act as antagoni sts of the T cell receptor (TCR). TCR antagonism appears to be associa ted with engagement of the TCR below a crucial affinity threshold nece ssary for full T cell activation. Studies addressing the molecular mec hanism of this effect suggest that TCR antagonists could act by interf ering with membrane-related events (such as proper receptor clustering ) that might precede intracellular signaling. Discovery of the TCR ant agonism phenomenon also suggested a possible rational approach to anti gen-specific immunointervention in allergies and autoimmune diseases. The feasibility of such an approach is now being actively investigated . Finally, TCR antagonist peptides may provide a useful tool to probe TCR-peptide/MHC interactions involved in the process of thymic educati on.