Minor histocompatibility antigens in allogeneic hematopoietic cell transplantation

Purpose of review This review focuses on recent developments in the immunobiology of human minor H antigens. Recent findings Two novel male-specific minor H (H-Y) antigens, encoded by the RPS4Y and TMSB4Y genes, have been added to the number of molecularly characterized human minor H antigens. Antibody responses to several Y chromosome genes that encode T-cell-defined minor H antigens have been detected in male recipients of hematopoietic cell grafts from major histocompatibility complex (MHC)-matched female donors, and correlate with both chronic graft-versus-host disease and long-term remission of disease. Cellular and molecular dissection of graft-versus-tumor (GVT) reactions occurring in allogeneic hematopoietic cell transplant recipients shows that GVT activity is probably mediated by a diverse ensemble of effector cells involving both the cellular and humoral arms of the immune system, and is directed at both polymorphic and nonpolymorphic antigens on recipient tumor cells. Comprehensive analysis of common DNA variation in the human genome suggests that the total number of polymorphic minor H loci is likely to be quite large. Summary Studies of immune responses against minor H antigens in recipients of MHC-matched allogeneic hematopoietic cell transplant are providing the foundation for immune therapies that will separate GVT activity from graft-versus-host disease after allogeneic hematopoietic cell transplantation.