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

Tetsuya Nishida, Yoshiki Akatsuka, Yasuo Morishima, Nobuyuki Hamajima, Kunio Tsujimura, Kiyotaka Kuzushima, Yoshihisa Kodera, Toshitada Takahashi

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)629-635
Number of pages7
JournalBritish Journal of Haematology
Volume124
Issue number5
DOIs
Publication statusPublished - 01-03-2004

All Science Journal Classification (ASJC) codes

  • Hematology

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