The Journal of Experimental Medicine
3rd Skeletal Biology and Medicine Symposium
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Published online 27 May 2003 doi:10.1084/jem.20021925
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© Rockefeller University Press, 0022-1007/2003/6/1489 $5.00
The Journal of Experimental Medicine, Volume 197, Number 11, 1489-1500

Identification of a Polymorphic Gene, BCL2A1, Encoding Two Novel Hematopoietic Lineage-specific Minor Histocompatibility Antigens

Yoshiki Akatsuka1, Tetsuya Nishida1,3, Eisei Kondo1, Mikinori Miyazaki1, Hirohumi Taji2, Hiroatsu Iida4, Kunio Tsujimura1, Makoto Yazaki5, Tomoki Naoe3, Yasuo Morishima2, Yoshihisa Kodera6, Kiyotaka Kuzushima1 and Toshitada Takahashi1

1 Division of Immunology, Aichi Cancer Center Research Institute
2 Department of Hematology and Chemotherapy, Aichi Cancer Center Hospital, Nagoya 464-8681, Japan
3 Department of Molecular Medicine and Clinical Science, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
4 Department of Hematology, Meitetsu Hospital, Nagoya, Aichi 451-0052, Japan
5 Department of Pediatrics, Nagoya City Moriyama Municipal Hospital, Nagoya 463-8567, Japan
6 Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya 453-0046, Japan

Address correspondence to Yoshiki Akatsuka, Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. Phone: 81-52-762-6111; Fax: 81-52-763-5233; E-mail: yakatsuk{at}aichi-cc.jp

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.

Key Words: minor histocompatibility antigen • hematopoietic cell transplantation • cytotoxic T lymphocyte • graft-versus-leukemia effect • linkage analysis


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