Khanna R, Burrows S R, Kurilla M G, Jacob C A, Misko I S, Sculley T B, Kieff E, Moss D J
Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
J Exp Med. 1992 Jul 1;176(1):169-76. doi: 10.1084/jem.176.1.169.
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.
人们对设计一种针对普遍存在的爱泼斯坦-巴尔病毒（EBV）的有效疫苗有着浓厚兴趣。EBV特异性细胞毒性T淋巴细胞（CTL）在清除病毒感染细胞中所起的重要作用已得到充分证实。使用少数免疫供体进行的有限研究已确定了EBV潜伏抗原内的靶表位。本研究对EBV编码蛋白中I类限制性CTL表位的分布进行了广泛分析。利用编码单个EBV潜伏抗原（爱泼斯坦-巴尔核抗原[EBNA]1、2、3A、3B、3C、LP和LMP 1）的重组痘苗病毒，我们成功定位了来自一组14名EBV免疫供体的CTL克隆所识别的靶表位。在定位的20个CTL表位中，有5个在肽水平上得到了确定。虽然针对9个表位的CTL克隆既能识别1型转化体也能识别2型转化体，但大量表位（在确定了EBV类型特异性的16个表位中有7个）仅在1型EBV转化体上被检测到。编码EBNA 3A和EBNA 3C的痘苗重组体比本研究中使用的任何其他痘苗重组体被识别的频率更高，而在EBNA 1中未定位到CTL表位。令人惊讶的是，尽管本研究中使用的痘苗重组体编码了EBV的大多数潜伏抗原，但大量EBV特异性CTL克隆的表位特异性无法定位。这些结果表明，任何基于CTL表位设计以提供广泛保护的EBV疫苗不仅需要包括潜伏抗原序列，还需要包括基因组的其他区域。人类CTL显然无法将EBNA 1识别为靶抗原，而EBNA 1通常是伯基特淋巴瘤和鼻咽癌中唯一表达的潜伏抗原，这表明除非潜伏抗原的下调能够被逆转，否则EBV特异性CTL对这些肿瘤的控制将不可行。
