Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies.
Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV-positive malignancies.
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DOI：
10.1084/jem.176.1.157
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发表时间：
1992-07-01
期刊：
影响因子：
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通讯作者：
Rickinson AB
中科院分区：
文献类型：
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作者：
Murray RJ;Kurilla MG;Brooks JM;Thomas WA;Rowe M;Kieff E;Rickinson AB
EB病毒(Epstein-Barr Virus，EBV)是一种具有致癌潜能的人类疱疹病毒，存在于B淋巴组织中，受病毒特异性细胞毒性T淋巴细胞(CTL)的监控。在体外重新激活时，这些CTL以HLAI类抗原限制性的方式识别EBV转化的淋巴母细胞系(LCL)，但为这种识别提供靶位的病毒抗原在很大程度上仍未确定。在这里，我们在合适的成纤维细胞靶点上测试了来自16个病毒免疫供体的EBV诱导的多克隆CTL制备，其中正常存在于LCL中的8个EBV潜伏蛋白(Epstein-Barr核抗原[EBNA]1、2、3A、3B、3C、领导蛋白[LP]和潜伏膜蛋白[LMP]1和2)已从重组痘苗病毒载体中单独表达。大多数捐献者对不同的病毒抗原有两种或两种以上的独立反应，表现出多组分反应。尽管精确的靶抗原选择明显受到供者的HLAI型的影响，但潜伏蛋白的子集，即EBNA 3A、3B和3C，在一系列的HLA背景上提供了主要的靶点；因此，16名捐赠者中有15名的CTL反应包含对这一亚组中的一种或多种蛋白质的反应性。对其他潜伏蛋白，即LMP-2和EBNA-2，我们通过特定的HLA决定簇检测到了反应的例子，但我们没有观察到对EBNA-1、EBNA-LP或LMP-1的反应性。一个供体的大量多克隆CTL反应以及其他供体的反应成分没有映射到任何已知的潜伏蛋白，这表明其他病毒靶抗原仍有待鉴定。这项工作对于对EBV阳性恶性肿瘤的CTL控制具有重要意义，在这种肿瘤中，病毒基因的表达往往限于特定的潜伏蛋白亚群。
Epstein-Barr virus (EBV), a human herpes virus with oncogenic potential, persists in B lymphoid tissues and is controlled by virus- specific cytotoxic T lymphocyte (CTL) surveillance. On reactivation in vitro, these CTLs recognize EBV-transformed lymphoblastoid cell lines (LCLs) in an HLA class I antigen-restricted fashion, but the viral antigens providing target epitopes for such recognition remain largely undefined. Here we have tested EBV-induced polyclonal CTL preparations from 16 virus-immune donors on appropriate fibroblast targets in which the eight EBV latent proteins normally found in LCLs (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, leader protein [LP], and latent membrane protein [LMP] 1 and 2) have been expressed individually from recombinant vaccinia virus vectors. Most donors gave multicomponent responses with two or more separate reactivities against different viral antigens. Although precise target antigen choice was clearly influenced by the donor's HLA class I type, a subset of latent proteins, namely EBNA 3A, 3B, and 3C, provided the dominant targets on a range of HLA backgrounds; thus, 15 of 16 donors gave CTL responses that contained reactivities to one or more proteins of this subset. Examples of responses to other latent proteins, namely LMP 2 and EBNA 2, were detected through specific HLA determinants, but we did not observe reactivities to EBNA 1, EBNA LP, or LMP 1. The bulk polyclonal CTL response in one donor, and components of that response in others, did not map to any of the known latent proteins, suggesting that other viral target antigens remain to be identified. This work has important implications for CTL control over EBV-positive malignancies where virus gene expression is often limited to specific subsets of latent proteins.