Clinical potential of the HA-1 peptide, a minor histocompatibility antigen

Abstract

Minor histocompatibility (H) antigens are the targets of host versus graft (HVG), graft versus host (GVH) and graft versus leukaemia (GVL) immune responses following transplantation of organs or tissues between donor/recipient pairs matched for transplantation antigens encoded by the major histocompatibility complex (MHC: HLA in humans). There is a particular clinical problem in predicting and treating GVH disease, which occurs in a significant proportion of bone marrow transplant (BMT) patients, even those with HLA-identical sibling donors. However, many of these recipients receive BMT as part of the treatment for leukaemia and there is a correlation in them between harmful GVH and potentially therapeutic GVL, implying the same target antigens. The molecular identity of minor H antigens is therefore a key issue. This patent describes the recent identification of one of the human minor H antigen (HA-1) and proposes methods for using the nonameric peptide identified, VLHDDLLEA, or analogues of it, to modulate HVG and GVH responses, to promote GVL and, with knowledge of the polymorphism of the encoding gene, to type BMT recipients and their potential donors for presence of the antigen.

• expression cloning
• graft versus host disease
• graft versus leukaemia
• major histocompatibility antigens
• minor histocompatibility antigens
• minor histocompatibility genes
• minor histocompatibility peptide epitopes
• T-lymphocytes
• transplantation