Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.
Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.
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DOI：
10.1084/jem.176.1.169
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发表时间：
1992-07-01
期刊：
影响因子：
--
通讯作者：
Moss DJ
中科院分区：
文献类型：
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作者：
Khanna R;Burrows SR;Kurilla MG;Jacob CA;Misko IS;Sculley TB;Kieff E;Moss DJ
设计针对普遍存在的EB病毒（EBV）的有效疫苗具有相当大的兴趣。EB病毒特异性细胞毒性T淋巴细胞（CTL）在消除病毒感染的细胞中的重要作用已得到充分证实。使用少量免疫供体的有限研究已经确定了EBV潜伏抗原内的靶表位。本研究提供了一个广泛的分析I类限制性CTL表位内EBV编码的蛋白质的分布。使用编码单个EBV潜伏抗原（Epstein-巴尔核抗原[EBNA] 1、2、3A、3B、3C、LP和LMP 1）的重组牛痘，我们成功地定位了来自一组14个EBV免疫供体的CTL克隆识别的靶表位。在定位的20个CTL表位中，5个在肽水平上被定义。尽管对9个表位具有特异性的CTL克隆识别1型和2型转化体，但仅在1型EBV转化体上检测到显著数量的表位（确定EBV类型特异性的16个表位中的7个）。编码EBNA 3A和EBNA 3C的牛痘重组体比本研究中使用的任何其他牛痘重组体更频繁地被识别，而没有CTL表位定位于EBNA 1中。令人惊讶的是，大量的EBV特异性CTL克隆的表位特异性不能本地化，虽然在这项研究中使用的重组痘苗病毒编码的大部分潜伏抗原的EBV。这些结果表明，任何基于CTL表位的EBV疫苗设计提供广泛的保护，将需要不仅包括潜伏抗原序列，而且还包括基因组的其他区域。人CTL明显不能识别EBNA 1作为靶抗原，EBNA 1通常是伯基特淋巴瘤和鼻咽癌中表达的唯一潜伏抗原，这表明除非潜伏抗原的下调可以逆转，否则EBV特异性CTL控制这些肿瘤将是不可行的。
There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein- Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.