Bogedain C, Wolf H, Modrow S, Stuber G, Jilg W
Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensburg, Germany.
J Virol. 1995 Aug;69(8):4872-9. doi: 10.1128/JVI.69.8.4872-4879.1995.
We identified the immediate-early transactivator Zta of Epstein-Barr virus as a target for specific cytotoxic T lymphocytes (CTL). Cells pulsed with overlapping synthetic peptides representing the entire amino acid sequence of Zta proved to be efficient for the in vitro stimulation of Zta-specific CTL in several donors. With peptide-pulsed target cells, we found that CTL from several donors recognize a peptide comprising 15 amino acids. The immune response against this peptide exerted by CTL lines from different donors was found to be restricted by two different molecules of the major histocompatibility complex: HLA-B8 and HLA-Cw6. The latter molecule could for the first time be identified as a restricting element for a CTL response. The epitope of the HLA-B8-restricted CTL could be mapped to an octameric sequence between amino acid positions 190 and 197 of the Zta protein, whereas the minimal epitope of HLA-Cw6-restricted CTL consists of 11 to 15 residues between positions 187 and 201. Thus, the HLA-B8 and HLA-Cw6 epitopes widely overlap but are not completely identical. In vitro stimulation of blood lymphocytes from a panel of HLA-B8-positive or HLA-Cw6-positive virus carriers, using autologous cells pulsed with the Zta peptides comprising the HLA-B8 or HLA-Cw6 epitope, respectively, revealed in both cases that most of these donors developed a Zta-specific cytotoxic activity. These data, as well as the high spread of the major histocompatibility complex molecules HLA-B8 and HLA-Cw6 in most populations, suggest that an efficient CTL response directed against gene products of the immediate-early group of the lytic cycle exists in vivo in a considerable portion of virus carriers. A CTL response against proteins expressed immediately after the switch into the lytic cycle could eliminate lytically activated cells at an early stage and would thus efficiently prevent the production and release of progeny virions.
我们将爱泼斯坦-巴尔病毒的立即早期反式激活因子Zta鉴定为特异性细胞毒性T淋巴细胞（CTL）的靶标。用代表Zta完整氨基酸序列的重叠合成肽脉冲处理的细胞，被证明能有效地在体外刺激多个供体的Zta特异性CTL。利用肽脉冲靶细胞，我们发现多个供体的CTL识别一种包含15个氨基酸的肽。来自不同供体的CTL系对该肽产生的免疫反应受主要组织相容性复合体的两种不同分子限制：HLA-B8和HLA-Cw6。后一种分子首次被鉴定为CTL反应的限制元件。HLA-B8限制的CTL的表位可定位到Zta蛋白氨基酸位置190至197之间的一个八聚体序列，而HLA-Cw6限制的CTL的最小表位由位置187至201之间的11至15个残基组成。因此，HLA-B8和HLA-Cw6表位广泛重叠但并不完全相同。分别用包含HLA-B8或HLA-Cw6表位的Zta肽脉冲处理自体细胞，对一组HLA-B8阳性或HLA-Cw6阳性病毒携带者的血液淋巴细胞进行体外刺激，结果在两种情况下均显示，这些供体中的大多数都产生了Zta特异性细胞毒性活性。这些数据，以及主要组织相容性复合体分子HLA-B8和HLA-Cw6在大多数人群中的高传播率，表明在相当一部分病毒携带者体内存在针对裂解周期立即早期基因产物的有效CTL反应。针对进入裂解周期后立即表达的蛋白质的CTL反应可以在早期消除裂解激活的细胞，从而有效地阻止子代病毒粒子的产生和释放。
