Antigen analogs/MHC complexes as specific T cell receptor antagonists

Annu Rev Immunol. 1994;12:413-31. doi: 10.1146/annurev.iy.12.040194.002213.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Antigens / chemistry*
  • Humans
  • Immune Tolerance / physiology
  • Major Histocompatibility Complex*
  • Models, Biological
  • Receptors, Antigen, T-Cell / antagonists & inhibitors*
  • Signal Transduction / immunology


  • Antigens
  • Receptors, Antigen, T-Cell