An analysis of functional T cell recognition sites on I-E molecules

Abstract

The recognition of I-E molecules by antigen-specific T cells was studied to determine if one or multiple topographic sites on the I-E molecules can function as restricting elements for T cells. A panel of 14 I-Ek-specific monoclonal antibodies (mAb) was used to inhibit T cell proliferation induced by antigens, the recognition of which was restricted by I-E-encoded determinants. These antibodies gave patterns of inhibition that were similar for three long-term antigen-specific T cell lines. Multiple distinct patterns of inhibition, however, were observed when a series of antigen-specific I-E-restricted T cell clones was studied. Differences were identified even among clones expressing apparently similar antigen specificities and MHC restriction. The observed inhibition by these antibodies appeared to be caused by specific steric or allosteric interference with T cell recognition of antigen and Ia. Based on the differences in patterns of inhibition, it was possible to infer the existence of distinct sites or conformations on the I-E molecule that are functionally involved in antigen-specific T cell recognition.