Functional separation in vivo of both antigens encoded by H–2 subregion and non-H–2 loci

Abstract

ANTIGENS coded for by the H–2K, H–2D and H–2I region of the major histocompatibility complex (MHC) of the mouse initiate different in vitro responses. I region-coded antigens activate mainly Lyt 1⁺ T cells to produce a proliferative response in mixed lymphocyte cultures (MLC), whereas K and D region-coded antigens predominantly stimulate Lyt 2⁺ T cells to become cytolytic effector cells¹. Proliferative responses in MLC and generation of cytolytic T cells in vitro can also be induced by minor histocompatibility antigens. For example, Mls-locus products can induce positive MLC responses, but not the generation of cytolytic T cells², whereas H–Y antigen does give rise to anti-H–Y cytotoxic T-cell responses in vitro, following in vivo priming³. Functional in vivo studies have shown that H–2K, H–2D and H–2I differences can account for graft rejection⁴ and for mortality in graft-versus-host (GvH) reactions⁵. Differences in only minor histocompatibility antigens are sufficient to cause graft rejection⁶, and lethal GvH reaction after allogeneic bone marrow transplantation⁷. Similarly, immunisation with only H–2 or only non-H–2 antigens can induce a state of delayed-type hypersensitivity (DTH) to the immunising antigen, which can be measured with the footpad swelling test⁸. So far, such in vivo experiments have shown little or no discrimination between responses to H–2 subregion antigens and responses to non-H–2 antigens. We have used a DTH assay to study the occurrence of T-effector cells after in vivo immunisation with different histocompatibility antigens. We show here that DTH T-effector cells generated in GvH and host-versus-graft (HvG) reactions are specific for largely different sets of histocompatibility antigens, with selective stimulation by H–2I and Mls-locus antigens in GvH conditions.