Clinical relevance of a newly identified HLA-A24-restricted minor histocompatibility antigen epitope derived from BCL2A1, ACC-1, in patients receiving HLA genotypically matched unrelated bone marrow transplant

Minor histocompatibility antigens (mHAs) are major histocompatibility complex (MHC)-associated peptides, which trigger T-cell responses that mediate graft versus host disease (GVHD) and graft versus leukaemia effects. We recently identified a new mHA epitope, termed ACC-1, which is presented by HLA-A(star)2402 and encoded by BCL2A1, whose expression is restricted to haematopoietic cells including leukaemic cells. HLA-A24/ACC-1 tetramer detected the presence of ACC-1-specific CD8(+) cells in the peripheral blood of a patient up to 7 months following transplantation, and these tetramer-positive cells were expandable in vitro by ACC-1 peptide stimulation. A retrospective analysis of 320 patients with HLA-A(star)2402 who had received a human leucocyte antigen (HLA) genotypically matched unrelated donor through the Japan Marrow Donor Programme was conducted to determine whether ACCA disparity is associated with adverse clinical outcomes such as GVHD. Among these patients, ACCA disparity was detected in 55 (17.2%) donor/recipient pairs. After adjusting for known risk factors, the hazard ratios or odds ratios of acute and chronic GVHD, relapse and disease-free survival were not statistically different between patients receiving ACC-1 compatible and incompatible transplantation. These data suggest that disparity of haematopoietic cell-specific mHA, ACCA, is unlikely at least to augment GVHD, and that T cells specific for ACC-1 may also be used for immunotherapy of recurring leukaemia without GVHD.