T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.
T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.
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DOI：
10.1084/jem.179.4.1297
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发表时间：
1994-04-01
影响因子：
15.3
通讯作者：
Masucci, M G
中科院分区：
文献类型：
--
作者：
de Campos-Lima, P O;Levitsky, V;Brooks, J;Lee, S P;Hu, L F;Rickinson, A B;Masucci, M G
Epstein-Barr 病毒 (EBV) 是一种人类 B 淋巴细胞疱疹病毒，可引发强烈的 HLA I 类限制性细胞毒性 T 淋巴细胞 (CTL) 反应。我们的发现首先表明了这种反应对病毒进化的影响，即来自 HLA A11 高度阳性巴布亚新几内亚 (PNG) 群体的 EBV 分离株在核抗原 EBV 编码的核抗原 (EBNA4) 的 424 残基处携带 lys-thr 突变，该突变破坏了 A11 限制性 CTL 识别的免疫显性靶表位。在这里，我们转向一个更大的人群，中国南方人，A11 等位基因再次存在于超过 50% 的个体中。从该群体中分析的 23 个 EBV 分离株中的每一个也在 EBNA4 416-424 表位中发生突变，这些突变选择性地涉及对于 A11-肽相互作用至关重要的位置 2（417 val-leu）或 9（424 lys-asp、-arg 或 -thr）中的两个锚定残基之一。大多数中国分离株和所有 10 个 PNG 分离株还携带影响下一个最具免疫优势的 A11 限制性表位（EBNA4 残基 399-408）的位置 1 和 2 的突变。这些变化明显影响了抗原性，因为携带这些突变 EBV 毒株的 A11 阳性淋巴母细胞系 (LCL) 不被针对原型 B95.8 病毒产生的 A11 限制性 CTL 识别。此外，自然感染这些突变病毒的中国供体在用携带 B95.8 或其内源 EBV 毒株的自体 LCL 细胞进行体外刺激时，没有产生可检测到的 A11 限制性 CTL 反应。因此，在两个不同的高度 A11 阳性群体中，免疫压力似乎选择了缺乏免疫显性 A11 限制性 CTL 表位的常驻 EBV 毒株。
Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11- positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11- restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399- 408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11- positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.