Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infection
Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infection
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DOI：
10.1089/104454902760330219
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发表时间：
2002-09-01
影响因子：
3.1
通讯作者：
Altfeld, M
中科院分区：
文献类型：
--
作者：
Addo, MM;Yu, XG;Altfeld, M
HIV-1调节蛋白达特和Rev以及辅助蛋白Vpr、Vpu和Vif对于病毒复制是必需的，并且它们的细胞质产生表明它们应该被细胞毒性T淋巴细胞处理以识别。然而，只有有限的数据是可用的，以评估在何种程度上这些蛋白质的目标在自然感染和最佳的细胞毒性T淋巴细胞（CTL）表位内的这些蛋白质还没有被定义。在这项研究中，针对HIV-1达特，Rev，Vpr，Vpu，和Vif的CTL反应进行了分析，在70个HIV-1感染的个人和10个HIV-1阴性对照使用重叠肽跨越整个蛋白质。通过Elispot测定和基于流动的细胞内细胞因子定量来测量肽特异性干扰素-γ（IFN-γ）产生。在分离肽特异性CD 8 + T细胞系后证实了HLA I类限制和细胞毒活性。所有调节蛋白和辅助蛋白都作为HIV-1特异性CTL的靶点，并且在这些蛋白的功能重要区域中鉴定出多个CTL表位。在某些个体中，对这些辅助和调节蛋白的HIV-1特异性CD 8 + T细胞应答占总HIV-1特异性CTL应答的三分之一。这些数据表明，尽管这些蛋白质的小尺寸的调节和辅助蛋白是由CTL在自然HIV-1感染的目标，并作出重要贡献的总HIV-1特异性的CD 8 + T细胞反应。这些发现是相关的急性和慢性感染期间的免疫反应的特异性和广度的评价，并将是有用的候选人的设计和测试的人类免疫缺陷病毒（HIV）疫苗。
The HIV-1 regulatory proteins Tat and Rev and the accessory proteins Vpr, Vpu, and Vif are essential for viral replication, and their cytoplasmic production suggests that they should be processed for recognition by cytotoxic T lymphocytes. However, only limited data is available evaluating to which extent these proteins are targeted in natural infection and optimal cytotoxic T lymphocyte (CTL) epitopes within these proteins have not been defined. In this study, CTL responses against HIV-1 Tat, Rev, Vpr, Vpu, and Vif were analyzed in 70 HIV-1 infected individuals and 10 HIV-1 negative controls using overlapping peptides spanning the entire proteins. Peptide-specific interferon-gamma (IFN-gamma) production was measured by Elispot assay and flow-based intracellular cytokine quantification. HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8+ T-cell lines. All regulatory and accessory proteins served as targets for HIV-1-specific CTL and multiple CTL epitopes were identified in functionally important regions of these proteins. In certain individuals HIV-1-specific CD8+ T-cell responses to these accessory and regulatory proteins contributed up to a third to the magnitude of the total HIV-1-specific CTL response. These data indicate that despite the small size of these proteins regulatory and accessory proteins are targeted by CTL in natural HIV-1 infection, and contribute importantly to the total HIV-1-specific CD8+ T-cell responses. These findings are relevant for the evaluation of the specificity and breadth of immune responses during acute and chronic infection, and will be useful for the design and testing of candidate human immunodeficiency virus (HIV) vaccines.