Minor transplantation antigens: mouse models for human host-versus-graft, graft-versus-host and graft-versus-leukemia...

Minor transplantation or histocompatibility (H) antigens are barriers to the transplantation of organs and tissues between genetically non-identical individuals who are matched for transplantation antigens encoded by the major histocompatibility complex (MHC), H2 in mice and HLA in humans. Recognition of minor H antigens by T cells can lead to host-versus-graft (HvG) rejection of organs and, in bone marrow transplantation, to life threatening graft-versus-host (GvH) reactions, although if these can be controlled, clinically useful graft-versus-leukemia (GvL) reactions can be obtained. This review describes the early in vivo studies that laid the foundations of our understanding that minor H antigens are the product of genetic polymorphisms, the subsequent in vitro work which has identified these at the molecular level as peptides presented to T cells by self MHC molecules, and the most recent developments, which have seen the use of minor H specific T cells clones and sophisticated biochemical and molecular biological approaches to identify genes encoding them.