Human cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses.
Human cytotoxic T-cell responses against Epstein-Barr virus nuclear antigens demonstrated by using recombinant vaccinia viruses.
复制标题
使用重组痘苗病毒证明了针对 Epstein-Barr 病毒核抗原的人类细胞毒性 T 细胞反应。
DOI：
10.1073/pnas.87.8.2906
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发表时间：
1990
影响因子：
11.1
通讯作者：
Kieff,E
中科院分区：
文献类型：
--
作者：
Murray,RJ;Kurilla,MG;Griffin,HM;Brooks,JM;Mackett,M;Arrand,JR;Rowe,M;Burrows,SR;Moss,DJ;Kieff,E
EB病毒是一种具有细胞生长转化潜能的B淋巴因子，通过病毒特异性细胞毒性T淋巴细胞(CTL)的监测，EB病毒感染的潜在致病效应被包含在健康病毒携带者身上。这种CTL反应针对的靶抗原尚不确定，但这些抗原可能来自病毒转化的B细胞中组成性表达的一种或多种EBV“潜伏”蛋白。我们分析了来自两个EBV免疫供体的CTL反应的靶向性，这两个供体对A型转化的自体细胞有优先反应，而对B型病毒分离株没有反应。在痘苗病毒启动子P7.5的控制下，将EBV核抗原(EBNA)EBNA 2、EBNA 3a、EBNA 3c和EBNA先导蛋白四种在A、B病毒类型之间具有等位基因多态性的EBV潜伏蛋白的编码序列导入痘苗病毒载体，并在相应的靶细胞中表达相应的EBNA蛋白。因此，来自一个供体的CTL反应被映射到A型EBNA 2蛋白，来自第二个供体的CTL反应被映射到A型EBNA 3a蛋白。此后，构建了一系列在EBNA 2 A型编码序列中携带特定内部缺失的重组痘苗病毒；通过使用这些载体，上述EBNA 2 A型特异性CTL反应被证明是针对蛋白质N末端附近100个氨基酸片段中的一个表位的。这项工作清楚地展示了人类CTL对EBV系统中病毒编码的核抗原的识别；此外，它建立了一种实验方法，可以扩展到所有EBV潜伏蛋白和更常见的与A型和B型病毒分离株交叉反应的CTL反应。
The potentially pathogenic effects of infection with Epstein-Barr virus (EBV), a B-lymphotropic agent with cell growth-transforming potential, are contained in healthy virus carriers by virus-specific cytotoxic T-lymphocyte (CTL) surveillance. The target antigens against which such CTL responses are directed are yet undefined, but the antigens probably derived from one or more of the EBV "latent" proteins constitutively expressed in virus-transformed B cells. We have analyzed target specificity of CTL responses from two EBV-immune donors that are preferentially reactive against autologous cells transformed with type A but not with type B virus isolates. Coding sequences for four EBV latent proteins with allelic polymorphism between A and B virus types--namely, the EBV nuclear antigens (EBNAs) EBNA 2, EBNA 3a, EBNA 3c, and EBNA leader protein--have been introduced into vaccinia virus vectors under control of vaccinia promoter P7.5 and used to express relevant EBNA proteins in appropriate target cells. Thus the CTL response from one donor has been mapped to type A EBNA 2 protein and from a second donor to type A EBNA 3a protein. Thereafter, a series of recombinant vaccinia viruses were constructed that carried specific internal deletions within the EBNA 2 type A coding sequence; by using these vectors, the above EBNA 2 type A-specific CTL response was shown to be directed against an epitope within a 100-amino acid fragment near the N terminus of the protein. This work clearly shows human CTL recognition of virus-coded nuclear antigens in the EBV system; moreover, it establishes an experimental approach that can be extended to all EBV latent proteins and to the more common CTL responses that cross-react against type A and type B virus isolates.