T cell-mediated antigen presentation: a potential mechanism of infectious tolerance.

Abstract

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.