Immediate-early transactivator Rta of Epstein-Barr virus (EBV) shows multiple epitopes recognized by EBV-specific cytotoxic T lymphocytes
Immediate-early transactivator Rta of Epstein-Barr virus (EBV) shows multiple epitopes recognized by EBV-specific cytotoxic T lymphocytes
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DOI：
10.1128/jvi.72.11.8644-8649.1998
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发表时间：
1998-11-01
影响因子：
5.4
通讯作者：
Jilg, W
中科院分区：
文献类型：
--
作者：
Pepperl, S;Benninger-Döring, G;Jilg, W
我们分析了eb病毒（EBV）的即时-早期反激活子Rta作为特异性细胞毒性T淋巴细胞（CTL）靶点的作用，合成了覆盖Rta整个氨基酸序列的重叠肽板，并用于诱导和分析EBV阳性供者的特异性CTL反应。利用肽脉冲靶细胞，我们发现了分布在整个蛋白质序列中的9个不同的CTL表位。一个表位被HLA-A24限制在Rta蛋白的28 ~ 37个氨基酸位置之间的十聚体序列DYCNVLNKEF上，另一个表位被HLA-B18限制在Rta的同一区域（25 ~ 39个残基）上。另一个最小表位可以定位到位于134和142个氨基酸位置之间的非美性序列ATIGTAMYK；该肽受到HLA-A11的抑制。另外4个表位被证实受到HLA-A2、-A3、-B61和-Cw4的限制，位于Rta残基225和239、145和159、529和543以及393和407之间。分别。对于另外两个表位，目前只知道其在Rta蛋白中的位置（残基121 ~ 135和441 ~ 455）；他们确切的HLA限制模式还没有被确定。利用含有Rta基因的重组痘苗病毒感染的靶细胞，我们发现8个Rta特异性CTL中有6个在内源性加工后也能识别相应的肽。这些数据表明Rta是ebv特异性细胞毒性的重要靶点。加上最近发现的其他即时早期和早期蛋白也作为CTL靶点，它们揭示了裂解周期蛋白在ebv感染细胞的免疫识别中的作用。
We analyzed the immediate-early transactivator Rta of Epstein-Barr virus (EBV) for its role as a target for specific cytotoxic T lymphocytes (CTL), Panels of overlapping peptides covering the entire amino acid sequence of Rta were synthesized and used to induct and analyze specific CTL responses in EBV-positive donors. Using peptide-pulsed target cells, we found nine different CTL epitopes that are distributed over the entire protein sequence. One epitope restricted by HLA-A24 could he mapped to the decameric sequence DYCNVLNKEF between amino acid positions 28 and 37 of the Rta protein, A second epitope could he assigned to the same region of Rta (residues 25 to 39) and was shown to be restricted by HLA-B18. Another, minimal epitope could be mapped to the nonameric sequence ATIGTAMYK between amino acid positions 134 and 142; this peptide was restricted by HLA-A11. Another four epitopes were proven to be restricted by HLA-A2, -A3, -B61, and -Cw4 and were located between Rta residues 225 and 239, 145 and 159, 529 and 543, and 393 and 407. respectively. For two other epitopes, only the location within the Rta protein is known so far (residues 121 to 135 and 441 to 455); their exact HLA restriction patterns have not get been identified. Using target cells infected with recombinant vaccinia virus containing the gene for Rta, we showed that six of eight Rta-specific CTL lints recognized the corresponding peptides also after endogenous processing. These data suggest that Rta comprises an important target for EBV-specific cellular cytotoxicity. Together with recent findings of other immediate-early and early proteins also acting as CTL targets, they reveal the role of proteins of the lytic cycle in the immune recognition of EBV-infected cells.