A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia.
A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia.
复制标题
DOI：
10.1084/jem.189.2.301
复制
发表时间：
1999-01-18
期刊：
影响因子：
--
通讯作者：
van de Wiel-van Kemenade E
中科院分区：
文献类型：
--
作者：
Dolstra H;Fredrix H;Maas F;Coulie PG;Brasseur F;Mensink E;Adema GJ;de Witte TM;Figdor CG;van de Wiel-van Kemenade E
人类次要组织相容性抗原（minor histocompatibility antigens，mHags）在人类组织相容性白细胞抗原（human histocompatibility leukocyte antigen，HLA）相合的异基因骨髓移植（alloy marrow transplantation，BMT）后诱导细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）抗白血病反应中起重要作用。由于大多数mHag不是白血病特异性的，但也由正常组织表达，因此抗白血病反应性通常与危及生命的移植物抗宿主病（GVHD）相关。在这里，我们描述了一种新的mHag，HB-1，增强供者来源的CTL反应性的B细胞急性淋巴细胞白血病（B-ALL）患者治疗HLA匹配的BMT。我们鉴定了编码HB-1特异性CTL识别的抗原肽的基因。有趣的是，HB-1基因的表达仅在B-ALL细胞和EB病毒转化的B细胞中观察到。HB-1基因编码的肽EEKRGSLHVW被与HLA-B44相关的CTL识别。进一步的分析表明，HB-1基因中的多态性在该肽内的位置8处产生从His到Tyr的单个氨基酸交换。这种氨基酸取代对于HB-1特异性CTL的识别至关重要。B-ALL细胞对多态性HB-1 Ag的限制性表达和使用负载肽的树突状细胞在体外产生HB-1特异性CTL的能力提供了特异性靶向免疫系统对抗B-ALL而没有诱发GVHD的风险的新机会。
Human minor histocompatibility antigens (mHags) play an important role in the induction of cytotoxic T lymphocyte (CTL) reactivity against leukemia after human histocompatibility leukocyte antigen (HLA)-identical allogeneic bone marrow transplantation (BMT). As most mHags are not leukemia specific but are also expressed by normal tissues, antileukemia reactivity is often associated with life-threatening graft-versus-host disease (GVHD). Here, we describe a novel mHag, HB-1, that elicits donor-derived CTL reactivity in a B cell acute lymphoblastic leukemia (B-ALL) patient treated by HLA-matched BMT. We identified the gene encoding the antigenic peptide recognized by HB-1–specific CTLs. Interestingly, expression of the HB-1 gene was only observed in B-ALL cells and Epstein-Barr virus–transformed B cells. The HB-1 gene–encoded peptide EEKRGSLHVW is recognized by the CTL in association with HLA-B44. Further analysis reveals that a polymorphism in the HB-1 gene generates a single amino acid exchange from His to Tyr at position 8 within this peptide. This amino acid substitution is critical for recognition by HB-1–specific CTLs. The restricted expression of the polymorphic HB-1 Ag by B-ALL cells and the ability to generate HB-1–specific CTLs in vitro using peptide-loaded dendritic cells offer novel opportunities to specifically target the immune system against B-ALL without the risk of evoking GVHD.