Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens

Yoshiki Akatsuka, Tetsuya Nishida, Eisei Kondo, Mikinori Miyazaki, Hirohumi Taji, Hiroatsu Iida, Kunio Tsujimura, Makoto Yazaki, Tomoki Naoe, Yasuo Morishima, Yoshihisa Kodera, Kiyotaka Kuzushima, Toshitada Takahashi

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

We report the identification of two novel minor histocompatibility antigens (mHAgs), encoded by two separate single nucleotide polymorphisms on a single gene, BCL2A1, and restricted by human histocompatibility leukocyte antigen (HLA)-A*2402 (the most common HLA-A allele in Japanese) and B*4403, respectively. Two cytotoxic T lymphocyte (CTL) clones specific for these mHAgs were first isolated from two distinct recipients after hematopoietic cell transplantation. Both clones lyse only normal and malignant cells within the hematopoietic lineage. To localize the gene encoding the mHAgs, two-point linkage analysis was performed on the CTL lytic patterns of restricting HLA-transfected B lymphoblastoid cell lines obtained from Centre d'Etude du Polymorphisme Humain. Both CTL clones showed a completely identical lytic pattern for 4 pedigrees and the gene was localized within a 3.6-cM interval of 15q24.3-25.1 region that encodes at least 46 genes. Of those, only BCL2A1 has been reported to be expressed in hematopoietic cells and possess three nonsynonymous nucleotide changes. Minigene transfection and epitope reconstitution assays with synthetic peptides identified both HLA-A*2402- and B*4403-restricted mHAg epitopes to be encoded by distinct polymorphisms within BCL2A1.

Original languageEnglish
Pages (from-to)1489-1500
Number of pages12
JournalJournal of Experimental Medicine
Volume197
Issue number11
DOIs
Publication statusPublished - Jun 2 2003

Keywords

  • Cytotoxic T lymphocyte
  • Graft-versus-leukemia effect
  • Hematopoietic cell transplantation
  • Linkage analysis
  • Minor histocompatibility antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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