Isolation of cytotoxic T lymphocytes from healthy seropositive individuals specific for peptide epitopes from Epstein-Barr virus nuclear antigen 1: Implications for viral persistence and tumor surveillance
Isolation of cytotoxic T lymphocytes from healthy seropositive individuals specific for peptide epitopes from Epstein-Barr virus nuclear antigen 1: Implications for viral persistence and tumor surveillance
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DOI：
10.1006/viro.1995.0076
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发表时间：
1995-12-20
期刊：
影响因子：
3.7
通讯作者：
Moss, DJ
中科院分区：
文献类型：
--
作者：
Khanna, R;Burrows, SR;Moss, DJ
Epstein-Barr 核抗原 1 (EBNA1) 是否包含细胞毒性 T 淋巴细胞 (CTL) 表位的问题引起了相当大的科学兴趣，主要是因为它对 Epstein-Barr 病毒 (EBV) 的整体生物学具有重要意义。早期研究表明，仅表达 EBNA1 的 EBV 相关恶性肿瘤可以逃避病毒特异性免疫监视，因为该抗原不是 CTL 识别的目标。在本报告中，我们使用了修改后的方案来证明 EBNA1 包含可以被多克隆和克隆 CTL 识别的序列。 CD4(+) CTL 克隆是从健康的血清阳性供体中分离出来的，该供体识别来自 EBNA1 的肽表位 TSLYNLRRGTALA 与 HLA DR1 相关。有趣的是，这些 CTL 无法裂解 EBV 感染的 B 细胞，这表明 EBNA1 可能不会被内源性加工和/或呈递给宿主 CTL 反应。尽管最近建议 EBNA1 内的甘氨酸-丙氨酸重复序列可以抑制内源性加工，但用编码截短的 EBNA1 蛋白的重组牛痘载体感染的靶细胞（没有这些重复序列）无法被该 CTL 克隆识别。因此，甘氨酸-丙氨酸重复序列的存在似乎并不抑制本研究中定义的 II 类限制性表位的加工。这些结果证实了这样的观点：EBV 感染的正常和恶性细胞（其中病毒基因表达仅限于 EBNA1）可以抵抗体内 CTL 介导的免疫监视。 (C) 1995 学术出版社
The question of whether Epstein-Barr nuclear antigen 1 (EBNA1) includes cytotoxic T lymphocyte (CTL) epitopes has generated considerable scientific interest, primarily due to its important implications for the overall biology of Epstein-Barr virus (EBV). Earlier studies have suggested that EBV-associated malignancies that express only EBNA1 escape virus-specific immune surveillance since this antigen is not a target for CTL recognition. In the present report we have used a modified protocol to demonstrate that EBNA1 includes sequences which can be recognized by both polyclonal and clonal CTLs. CD4(+) CTL clones were isolated from a healthy, seropositive donor that recognized the peptide epitope TSLYNLRRGTALA from EBNA1 in association with HLA DR1. Interestingly, these CTLs are unable to lyse EBV-infected B cells suggesting that EBNA1 may not be endogenously processed and/or presented to the host CTL response. Despite recent suggestions that glycine-alanine repeat sequences within EBNA1 can inhibit endogenous processing, target cells infected with recombinant vaccinia vectors encoding truncated EBNA1 proteins, without these repeat sequences, were not recognized by this CTL clone. Thus it seems that the presence of glycine-alanine repeats is not responsible for inhibiting the processing of the class II-restricted epitope defined in this study. These results substantiate the view that EBV-infected normal and malignant cells, where viral gene expression is limited to EBNA1, can resist CTL-mediated immune surveillance in vivo. (C) 1995 Academic Press, Inc.