T cell-mediated antigen presentation: a potential mechanism of infectious tolerance.
Differentiation of the T cell repertoire and the physiology of T cell-mediated antigen presentation are reviewed in relation to mechanisms of self-tolerance. Recent research has indicated that T cell development is a continual process that optimizes partial recognition of self as a homeostatic set-point. Specific T cell antigen recognition of partial agonists is intrinsically linked to expression of class II MHC glycoproteins on T cells. Even ligands that act as TCR antagonists in IL-2 production assays have sufficient agonistic strength to induce expression of class II MHC glycoproteins on T cells. Thus, the intrinsic self-reactivity of the T cell repertoire may promote T-APC activity in vivo and may explain why thymic and peripheral T cells express low but significant levels of class II MHC glycoproteins. T-APC activity induces extensive apoptosis among responder T cells, causes desensitization among surviving responders, and has been implicated in the adoptive transfer of tolerance in the Lewis rat model of experimental autoimmune encephalomyelitis. Overall, these findings support a relationship between the partial recognition of self MHC ligands, expression of class II MHC glycoproteins on mature peripheral T cells, tolerogenic T cell-mediated antigen presentation, and desensitization of pathogenic self-reactive T cells.
Mannie
M D
MD
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA. manniem@mail.ecu.edu
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D017634:Self Tolerance / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II