Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens.
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.
Akatsuka
Yoshiki
Y
Division of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. yakatsuk@aichi-cc.jp
Nishida
Tetsuya
T
Kondo
Eisei
E
Miyazaki
Mikinori
M
Taji
Hirohumi
H
Iida
Hiroatsu
H
Tsujimura
Kunio
K
Yazaki
Makoto
M
Naoe
Tomoki
T
Morishima
Yasuo
Y
Kodera
Yoshihisa
Y
Kuzushima
Kiyotaka
K
Takahashi
Toshitada
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D015234:HLA-A Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007564:Japan; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D008912:Minor Histocompatibility Loci; D008969:Molecular Sequence Data; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
C096816:BCL2-related protein A1; D018076:DNA, Complementary; D015234:HLA-A Antigens; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2