Human minor histocompatibility antigens: New concepts for marrow transplantation and adoptive immunotherapy

Bone marrow transplantation (BMT) is the present treatment for hematological malignancies. Two major drawbacks of allogeneic BMT are graft-versus-host disease (GVHD) and leukemia relapse. The use of HLA-matched siblings as marrow donors results in the best transplant outcome. Nonetheless, the results of clinical BMT reveal that the selection of MHC-identical donors' bone marrow (BM) is no guarantee for avoiding GVHD or ensuring disease-free survival even when donor and recipient are closely related. It is believed that non-MHC-encoded so-called minor histocompatibility antigens (mHag) are involved in both graft-versus-host and graft-versus-leukemia activities. The recent new insights into the chemical nature of mHag not only reveal their physiological function but, more importantly, provide insights into their role in BMT. Together with the information on the human mHag genetics and tissue distribution gathered in the past, we may now apply this knowledge to the benefit of human BMT. Directly relevant is the utility of mHag molecular typing for diagnostics in BM donor selection. Most promising is the use of mHag-specific cytotoxic T cells for adoptive immunotherapy of leukemia.