Antigen analogs/MHC complexes as specific T cell receptor antagonists.
Recent studies demonstrated that antigen analogs can act as powerful and specific inhibitors of T cell activation, leading to the formulation of the concept that antigen analog/MHC complexes may act as antagonists of the T cell receptor (TCR). TCR antagonism appears to be associated with engagement of the TCR below a crucial affinity threshold necessary for full T cell activation. Studies addressing the molecular mechanism of this effect suggest that TCR antagonists could act by interfering with membrane-related events (such as proper receptor clustering) that might precede intracellular signaling. Discovery of the TCR antagonism phenomenon also suggested a possible rational approach to antigen-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 education.
Cytel, San Diego, California 92121.
A
A
Sette
J
J
Alexander
J
J
Ruppert
K
K
Snoke
A
A
Franco
G
G
Ishioka
H M
HM
Grey
D000818:Animals; D000941:Antigens / Q000737:chemistry*; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D008285:Major Histocompatibility Complex; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000276:immunology
D000941:Antigens; D011948:Receptors, Antigen, T-Cell