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

Br J Haematol. 2004 Mar;124(5):629-35. doi: 10.1111/j.1365-2141.2004.04823.x.

Abstract

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*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*2402 who had received a human leucocyte antigen (HLA) genotypically matched unrelated donor through the Japan Marrow Donor Programme was conducted to determine whether ACC-1 disparity is associated with adverse clinical outcomes such as GVHD. Among these patients, ACC-1 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, ACC-1, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bone Marrow Transplantation / immunology*
  • Child
  • Child, Preschool
  • Epitopes
  • Female
  • Genes, BRCA2*
  • Graft vs Host Disease / genetics
  • Graft vs Leukemia Effect / genetics
  • HLA-A Antigens / genetics*
  • HLA-A24 Antigen
  • Hematologic Neoplasms / therapy
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Polymorphism, Genetic
  • Retrospective Studies
  • Risk Factors
  • T-Lymphocytes / immunology

Substances

  • Epitopes
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Minor Histocompatibility Antigens