Minor transplantation antigens: their role in shaping the T cell repertoire

Minor transplantation, or histocompatibility (H), antigens are the targets of host-versus-graft (hvg) and graft-versus-host (gvh) reactions that occur when organs or tissues are exchanged between members of the same species who, although genetically not identical, are matched for their major histocompatibility complex (MHC) encoded transplantation antigens. Genes encoding minor H antigens map outside the MHC, on a number of different chromosomes. Whilst gvh and hvg reactions against individual minor H antigens are relatively weak, certainly in comparison with such reactions against MHC antigens, the presence of multiple minor H differences (the situation encountered in man) gives rise to very vigorous reactions that can endanger the survival of graft or host, or both. This is the pathological role of minor H antigens and, indeed, it was this role which was first designated to the MHC antigens, before their physiological role as guidance molecules for T lymphocytes was discovered. Recently, a potential physiological role for minor H antigens has been uncovered by the finding that the presence of certain minor H alleles in mice leads to removal in the thymus (negative selection) of all those T cells expressing a particular T cell receptor (TCR) gene. Such cells therefore never reach the periphery, where they might otherwise give rise to autoimmune reactions. The T cell repertoire is thus moulded by at least some minor H antigens, which may therefore be regarded as non-MHC immune response genes. Furthermore, T cell receptor usage by T cells specific for allogeneic minor H antigens appears not to be representative of T cell receptor usage in the peripheral pool.(ABSTRACT TRUNCATED AT 250 WORDS)