T-Cell Recognition of Minor Lymphocyte Stimulating (MLS) Gene Products

The immune system has evolved with a highly diverse antigen-specific repertoire capable of recognizing an extraordinarily large universe of foreign antigens. As a corollary of this wide diversity, the precursor fre­ quency of T cells specific for any given foreign antigen is generally very low, so low, in fact, that proliferative responses of naive T-cell populations to these antigens are undetectable. However, prominent exceptions to this generalization have been identified. In multiple species, cell surface alloan­ tigens encoded by genes of the major histocompatibility complex (MHC) are recognized by T cells at a high precursor frequency and are capable of eliciting a strong proliferative mixed lymphocyte response by unprimed T­ cell populations ( 1 , 2). In the mouse, a second set of determinants, the minor lymphocyte stimulatory (Mis) determinants, also induce strong proliferative responses by naive T cells (3-5). The finding that T cells are reactive to MHC and to Mis determinants at extraordinarily high pre­ cursor frequencies (1 , 2, 6, 7) has generated interest in understanding the biologic significance of these two systems. A great deal of information has been accumulated concerning the structure and function of MHC genes and their products, and the biologic importance of MHC-encoded deter­ minants has been extensively documented (reviewed in 8). In contrast, although MIs gene products were described as lymphocyte