Cytotoxic T-lymphocyte responses to a polymorphic Epstein-Barr virus epitope identify healthy carriers with coresident viral strains
Cytotoxic T-lymphocyte responses to a polymorphic Epstein-Barr virus epitope identify healthy carriers with coresident viral strains
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DOI：
10.1128/jvi.74.4.1801-1809.2000
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发表时间：
2000-02-01
影响因子：
5.4
通讯作者：
Rickinson, AB
中科院分区：
文献类型：
--
作者：
Brooks, JM;Croom-Carter, DSG;Rickinson, AB
细胞毒性 T 淋巴细胞 (CTL) 对 Epstein-Barr 病毒 (EBV) 的反应往往集中在少数免疫显性病毒表位上；当这些表位序列在 EBV 毒株之间具有多态性时，宿主 CTL 特异性应反映驻留毒株的身份。在研究 HLA-B27 阳性病毒携带者的反应时，我们鉴定了 15 名个体中的 2 名，他们对来自核抗原 EBNA3C 的泛 B27 表位 RRIYDLIEL (RRIY) 有很强的 CTL 记忆，但其体外分离的内源 EBV 株编码变异序列 RKIYDLIEL (RKIY)，该序列不能与 B27 分子形成稳定的复合物，并且很难被 RRIY 特异性 CTL 识别。为了检查这些个体是否也携带表位阳性毒株（与体外分离株相关或不同），我们从新鲜分离的外周血单核细胞中筛选 DNA，以寻找跨 EBNA3C 表位、跨 EBNA3C 具有 1 型-2 型序列分歧的不同区域以及跨 EBNA1 多态性区域的可扩增病毒序列。这表明其中一名不明原因的 RRIY 应答者携带两种不同的 1 型毒株，一种带有 RKIY，另一种带有 RRIY 表位序列。另一名应答者携带 RKIY 阳性 1 型毒株和 2 型病毒，其表位序列 RRIFDLIEL 与 RRIY 发生抗原交叉反应。通过此类检测分析，在 15 名 EBV 血清阳性供体中，12 名似乎携带单一病毒株，一名同时感染不同的 1 型病毒株，两名同时携带 1 型和 2 型病毒。这意味着一小部分但相当大比例的健康病毒携带者携带多种（可能是相继获得的）EB 病毒株。
Cytotoxic T-lymphocyte (CTL) responses to Epstein-Barr virus (EBV) tend to focus on a few immunodominant viral epitopes; where these epitope sequences are polymorphic between EBV strains, host CTL specificities should reflect the identity of the resident strain. In studying responses in HLA-B27-positive virus carriers, we identified 2 of 15 individuals who had strong CTL memory to the pan-B27 epitope RRIYDLIEL (RRIY) from nuclear antigen EBNA3C but whose endogenous EBV strain, isolated in vitro, encoded a variant sequence RKIYDLIEL (RKIY) which did not form stable complexes with B27 molecules and which was poorly recognized by RRIY-specific CTLs. To check if such individuals were also carrying an epitope-positive strain (either related to or distinct from the in vitro isolate), we screened DNA from freshly isolated peripheral blood mononuclear cells for amplifiable virus sequences across the EBNA3C epitope, across a different region of EBNA3C with type 1-type 2 sequence divergence, and across a polymorphic region of EBNA1. This showed that one of the unexplained RRIY responders carried two distinct type 1 strains, one with an RKIY and one with an RRIY epitope sequence. The other responder carried an RKIY-positive type 1 strain and a type 2 virus whose epitope sequence of RRIFDLIEL was antigenically cross-reactive with RRIY. Of 15 EBV-seropositive donors analyzed by such assays, 12 appeared to be carrying a single virus strain, one was coinfected with distinct type 1 strains, and two were carrying both type 1 and type 2 viruses. This implies that a small but significant percentage of healthy virus carriers harbor multiple, perhaps sequentially acquired, EBV strains.