DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells
DDX3Y encodes a class I MHC-restricted H-Y antigen that is expressed in leukemic stem cells
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DOI：
10.1182/blood-2007-06-096313
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发表时间：
2008-05-01
期刊：
影响因子：
20.3
通讯作者：
Warren, Edus H.
中科院分区：
文献类型：
--
作者：
Rosinski, Kellie V.;Fujii, Nobuharu;Warren, Edus H.
Y 染色体编码男性特异性次要组织相容性 (H-Y) 抗原，可在性别不匹配的同种异体造血细胞移植 (HCT) 后刺激 T 和 B 淋巴细胞反应。从一名接受了来自其人类白细胞抗原 (HLA) 相同姐妹的造血细胞移植物的男性中分离出一个 CD8(+) 细胞毒性 T 淋巴细胞 (CTL) 克隆，该克隆可识别由 DDX3Y 基因编码的新型 HLA-B*2705 限制性 H-Y 抗原。抗原肽是十聚体，与同源 DDX3X 编码的肽有 4 个位置不同。通过定量聚合酶链式反应 (PCR) 和 CTL 识别测定来检查 DDX3Y 及其编码的 H-Y 表位的表达。在携带完整 Y 染色体的所有骨髓和淋巴白血病细胞中均检测到 DDX3Y 的表达。此外，DDX3Y编码的H-Y表位存在于男性HLA-B*2705(+)患者的骨髓和淋巴白血病细胞的表面。 DDX3Y 特异性 CTL 可以防止人类急性白血病在非肥胖糖尿病/严重联合免疫缺陷小鼠中的植入，这表明 DDX3Y 编码的 H-Y 抗原也在白血病干细胞中表达。这些结果表明，在女性进入男性同种异体 HCT 后，针对 DDX3Y 的 CD8+ T 细胞反应有可能促进移植物抗白血病 (GVL) 活性。该研究在 http://clinicaltrials.gov 上注册为 NCT00107354。
The Y chromosome encodes male-specific minor histocompatibility (H-Y) antigens that stimulate T- and B-lymphocyte responses after sex-mismatched allogeneic hematopoietic cell transplantation (HCT). A CD8(+) cytotoxic T lymphocyte (CTL) clone that recognizes a novel HLA-B*2705-restricted H-Y antigen encoded by the DDX3Y gene was isolated from a male who had received a hematopoietic cell graft from his human leukocyte antigen (HLA)-identical sister. The antigenic peptide is a decamer that differs from the homologous DDX3X-encoded peptide at 4 positions. Expression of DDX3Y and of the H-Y epitope that it encodes was examined by quantitative polymerase chain reaction (PCR) and by CTL recognition assays. Expression of DDX3Y is detected in all myeloid and lymphoid leukemic cells that carry an intact Y chromosome. Moreover, the DDX3Y-encoded H-Y epitope is presented on the surface of both myeloid and lymphoid leukemic cells from male HLA-B*2705(+) patients. DDX3Y-specific CTLs prevent engraftment of human acute leukemia in nonobese diabetic/severe combined immune deficient mice, demonstrating that the DDX3Y-encoded H-Y antigen is also expressed in leukemic stem cells. These results demonstrate that CD8+ T-cell responses against DDX3Y have the potential to contribute to graft-versus-leukemia (GVL) activity after female into male allogeneic HCT. This study is registered at http://clinicaltrials.gov as NCT00107354.