Regulatory Mechanisms in Cell-mediated Immune

We have previously described the activation of a population of mixed leukocyte response suppressor T cells (MLR Ts) 1 by H-2-incompatible leukocytes. Reexposure of such cells to priming H-2 alloantigens in vitro triggers the release of a suppressor factor (MLR TsF) that prohibits alloantigen-induced T cell proliferation in the mixed leukocyte response (MLR) (1). Activated MLR Ts and MLR TsF characteristically express I-C alloantigens (2, 3); moreover I-C determinants restrict effective suppressor-responder cell interactions (4). Recent investigations have centered on the specific and perhaps unique requirements for the differentiation and proliferation of H-2 antigen-reactive MLR Ts. Two previous observations suggest that the MLR Ts population includes two general Ts subsets that recognize either class I (H-2K or H-2D) or class II (H-2I) alloantigens. Partial and additive TsF activity is elicited by individual H-2K and H-2D, as well as H-2I antigen-specific restimulation of an MLR Ts population primed against an entire H-2 haplotype difference (5). In addition, immunoadsorbent analyses indicate that MLR TsF forms complexes with shed stimulator cell antigens in the in vitro restimulation culture, and that these complexes, acting in an alloantigen-nonspecific fashion, represent the major suppressive species in MLR TsF preparations (S. Rich, manuscript in preparation). MLR TsF from Ts primed and restimulated against an entire H-2 complex difference can be isolated into H-2K, D, and I antigen-bound fractions by adsorption to insolubilized antibodies specific for individual stimulator H-2 region antigens. Together these data are consistent with a complex repertoire of H-2 class I and II antigen-specific MLR Ts and TsF. The present studies examine the role of individual H-2I subregion determinants in the activation of MLR Ts primed to antigens of the entire H-2I region, and their possible expression on those stimulator cells required to trigger primed