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

Identification of a polymorphic gene, BCL2A1, encoding two novel hematopoietic lineage-specific minor histocompatibility antigens.
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鉴定多态性基因BCL2A1,编码了两个新型的造血谱系特异性小型组织相容性抗原。

DOI:
10.1084/jem.20021925
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发表时间:
2003-06-02
影响因子:
15.3
通讯作者:
Takahashi, T
Takahashi, T
中科院分区:
医学1区
文献类型:
--
作者:
Akatsuka, Y;Nishida, T;Kondo, E;Miyazaki, M;Taji, H;Iida, H;Tsujimura, K;Yazaki, M;Naoe, T;Morishima, Y;Kodera, Y;Kuzushima, K;Takahashi, T

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我们报告了两种新型次要组织相容性抗原 (mHAgs) 的鉴定,它们由单个基因 BCL2A1 上的两个独立的单核苷酸多态性编码,并分别受到人类组织相容性白细胞抗原 (HLA)-A*2402(日本最常见的 HLA-A 等位基因)和 B*4403 的限制。在造血细胞移植后,首先从两个不同的受体中分离出对这些 mHAg 具有特异性的两个细胞毒性 T 淋巴细胞 (CTL) 克隆。两种克隆仅裂解造血谱系内的正常细胞和恶性细胞。为了定位编码 mHAgs 的基因,对从人类多态性研究中心获得的限制性 HLA 转染的 B 类淋巴母细胞系的 CTL 裂解模式进行了两点连锁分析。两个 CTL 克隆在 4 个谱系中均显示出完全相同的裂解模式,并且该基因位于 15q24.3-25.1 区域 3.6-cM 区间内,该区域编码至少 46 个基因。其中,据报道只有 BCL2A1 在造血细胞中表达并具有三个非同义核苷酸变化。使用合成肽进行小基因转染和表位重建测定,鉴定出 HLA-A*2402 和 B*4403 限制性 mHAg 表位由 BCL2A1 内的不同多态性编码。
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.
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发表时间: 1999-01-18
期刊: The Journal of experimental medicine
影响因子: --
作者:
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影响因子: 9.8
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发表时间: 1997-02-27
期刊: ONCOGENE
影响因子: 8
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DOI: 10.1097/01.tp.0000039166.86548.93
发表时间: 2002-12-27
期刊: TRANSPLANTATION
影响因子: 6.2
作者:
Akatsuka, Y;Kondo, E;Takahashi, T
通讯作者: Takahashi, T