Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation.

Abstract

The interaction of nominal Ag [antigen] with major histocompatibility complex (MHC)-restricted [mouse] T cells and accessory cells was studied by analyzing the effect of structurally related antigens on the response of antigen-specific MHC-restricted T cell hybridomas. The copolymer L-glutamic acid50-L-tyrosine50 (GT) completely inhibits the response of L-glutamic acid60-L-alanine40-L-tyrosine10 (GAT)-specific, I-Ad-restricted T cell hybridomas to GAT plus accessory cells. This inhibition is specific as hybridomas of other specificities are not inhibited under identical conditions; it is unique to the GT antigen as other similar copolymers are not inhibitory. The inhibitory effect is reversible by adding increasing amounts of GAT. Antigen-pulsing experiments localized the inhibition to the level of antigen-presenting cell (APC). GT-prepulsed APC are not inhibitory in cell-mixing experiments and can present other antigens. GT only inhibits the nominal antigen-directed component of a GAT-specific, autoreactive hybrid''s response. GT probably causes inhibition by competing for GAT association at the accessory cell. GT interferes with GAT presentation by an I-Adxb F1 APC to a BALB/c, I-Ad-restricted, but nt B10, I-Ab-restricted, T cell hybridoma; GT inhibits presentation by GAT-prepulsed APC. The implications of these findings for MHC-restricted presentation of antigen are discussed.