Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection
Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection
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DOI：
10.1128/jvi.72.5.3999-4004.1998
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发表时间：
1998-05-01
影响因子：
5.4
通讯作者：
Rothman, AL
中科院分区：
文献类型：
--
作者：
Mathew, A;Kurane, I;Rothman, AL
我们检查了从泰国患者自然症状继发登革热病毒感染后 12 个月获得的外周血单核细胞 (PBMC) 的记忆细胞毒性 T 淋巴细胞 (CTL) 反应。在所有分析的四名患者中，在批量培养的 PBMC 中检测到针对非结构性登革热病毒蛋白的 CTL，从两名患者 KPP94-037 和 KPP94-024 的批量培养中产生了许多 CD4(+) 和 CD8(+) CTL 系，它们分别对 NS1.2a（NS1 和 NS2a 统称）和 NS3 蛋白具有特异性。来自两名患者的所有 CTL 系均与登革热病毒的其他血清型发生交叉反应。来自患者KPP94-037的CD8(+) NS1.2a特异性细胞系是HLA B57限制性的，而来自患者KPP93-024的CD8(+) NS3特异性细胞系是HLA B7限制性的。来自患者 KPP94-037 的 CD4(+) CTL 系受到 HLA DR7 限制。从患者 KPP93-024 中分离出的大多数 CD8(+) CTL 能够识别 NS3 上的氨基酸 221 至 232。这些结果表明，在有症状的继发性自然登革热感染后的泰国患者中，CTL 主要针对非结构蛋白，并且具有广泛的交叉反应性。
We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins, Numerous CD4(+) and CD8(+) CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8(+) NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8(+) NS3-specific lines from patient KPP93-024 were HLA B7 restricted. The CD4(+) CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8(+) CTLs isolated from patient KPP93-024 were found to recognize amino acids 221 to 232 on NS3, These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.