Minor histocompatibility antigens: from transplantation problems to therapy of cancer

The idea of transferring healthy marrow for the therapeutic treatment of the various diseases of the blood and of the immune system made a significant contribution to controlling diseases and to advancing modern clinical sciences. The first series of bone marrow transplantations in the 1960s were confronted with severe complications. It became clear that matching for the human leukocyte antigen (HLA) system between donor and recipient significantly improved the clinical results. Nonetheless, an unacceptable percentage of severe complications remained that is mainly attributable to non-HLA histocompatibility systems, i.e., minor histocompatibility antigens. Observations in the 1970s that minor histocompatibility antigens cause serious problems in human bone marrow transplantation laid the basis for their use as curative antigens in stem cell transplantation to date. Thus, the allo-immune T cell activities caused by minor histocompatibililty antigen disparities between HLA-matched donor and recipient can now be applied for the benefit of the transplant patient.