T-Cells Recognize IA Conformation in the Interaction with Antigen Presenting Cells
The presentation of soluble antigens by antigen presenting cell (APC) to T-cells requires that the antigen be recognized in the context of an Ia determinant (Shevach and Rosenthal, 1973). Although the T cell antigen receptor has been identified and sequenced (Hedrick et al., 1984; Fink et al., 1986), the nature of the ligand that triggers the T cells remains unclear. The early experiments of Lin et al. (1981) and Michaelides et al. (1983) using the IA mutant strain of mouse B6.C-H-2 bml 2 (bm1 2) demonstrated that limited alteration of the Ia molecule concomitantly led to changes in the response pattern of T-cells to soluble antigens. Specifically, it was shown that bml 2 lost immune responsiveness to the antigens beef insulin and H-Y while their responses to other antigens remained normal when compared to the wild type C57BL/6. Besides providing convincing evidence equating Ia to the Ir gene product, these experiments also suggest that there are multiple funcitonal domains (Beck et al., 1983) on the Ia molecule that by some unknown mechanisms determine responsiveness to certain antigens. Indeed, this conclusion is consistent with other studies using a variety of approaches such as monoclonal antibody blocking (Frelinger et al., 1984), site-directed mutagenesis (Cohen et al., 1986), in vitro selection of variant APC lines (Glimcher et al., 1983b) and inhibition of specific antigen response with structurally related co-polymers (Benacerraf and Rock, 1984). More recently, Babbitt and coworkers (1985) using biochemical methods demonstrated a weak but measurable physical association between a hen egg lysozyme antigenic fragment and purified Ia molecules. This association was demonstrated for Ia derived from responder strains but not that from non-responder strains. In another analysis, Ashwell and Schwartz (1986) also provided arguments that antigen and Ia physically interacted to form a ternary complex recognizable by the T-cell antigen receptor.
KeywordsConformational Determinant Soluble Antigen Gene Conversion Event Bm12 Mutation Bm12 Mouse
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