Chimera Response to Minor Histocompatibility

Despite much recent interest and effort, the role played by major histocompatibility complex products in the regulation of T-cell responses remains perplexing. In 1972 it was observed that mouse T and B cells would only cooperate in an antibody reponse if they shared certain regions of H-2 (1). Subsequently, H-2 gene products were also found to be involved in cytotoxic Tcell reactions, and it was postulated that the killer T cell must bear H-2 molecules in common with those of its target in order to effect lysis (2-6). Later studies with radiation chimeras showed that this is not the case, but that the H2 region must be shared between the cells used to stimulate the response and the targets; a killer T cell that was itself H-2 type A, after having grown up in an (A × B)F1 could be stimulated to lyse H-2 type B virus-infected or trinitrophenyl-modified targets (7-9). Such chimeras were also found to contain A type helper T cells which can cooperate with B type B cells (10). It was then postulated that T-cell precursors "learn" to recognize the H-2 type of the host as self (11). Recent evidence shows that the host H-2 type of a chimera does distinctly influence the specificity of the responding T-cell population (12, 13) and that it is the H-2 type of the thymus that is important (13). Most of this work has been done with semiallogeneic chimeras (e.g., "A" bone marrow into an irradiated [A × B]F, or [A × B]F1 bone marrow into an "A" or [A × C]F1) where the responses were very strongly restricted by the H-2 type of the host. A small number of completely allogeneic chimeras was tested (e.g., "A" bone marrow into "B") and appeared to be immunoincompetent. The virtually absolute restriction of the semiallogeneic chimeras as well as the immunoincompetence of the fully allogeneic chimeras has led to much speculation and has been quoted as suggestive evidence for the dual recognition model of T-cell receptors (13). We report here that in contrast to the results with virus-infected mice, fully allogeneic chimeras made by repopulating irradiated BALB/c(H-2 d) mice with BALB.B(H-2 b) bone marrow are well able to respond to minor histocompatibility