Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells:: Correlation with viral load
Hierarchical targeting of subtype C human immunodeficiency virus type 1 proteins by CD8+ T cells:: Correlation with viral load
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DOI：
10.1128/jvi.78.7.3233-3243.2004
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Gray, CM
中科院分区：
文献类型：
--
作者：
Masemola, A;Mashishi, T;Gray, CM
理解T细胞表位应答的广度和幅度与病毒载量之间的关系对于设计有效的疫苗是重要的。在这项研究中，我们筛选了一组46个C亚型人类免疫缺陷病毒1型（HIV-1）感染的个体，针对一组对应于完整C亚型基因组的肽的T细胞应答。我们使用γ干扰素ELISPOT检测来探索跨表达的HIV-1基因组的T细胞应答模式与病毒控制相关的假设。该队列从血清转换到应答的估计中位时间为13个月，针对HIV蛋白的累积T细胞应答的顺序如下：Nef > Gag > Pol > Env > Vif > Rev > Vpr >达特> Vpu。Nef是最强的靶向蛋白，97.5%的表位聚集在119个氨基酸内，构成了整个表达基因组中几乎三分之一的反应。第二大靶向区域是p24，占响应的17%。病毒载量和反应幅度之间没有相关性，但病毒载量和反应总幅度之间存在弱正相关性（r = 0.297; P = 0.034），这意味着T细胞识别的幅度对病毒控制没有贡献。当识别的分级模式与病毒载量相关时，优先靶向Gag与病毒控制显著相关（r = 0.445; P = 0.0025）。这些数据表明，优先靶向Gag表位，而不是整个基因组的反应的广度或幅度，可能是免疫功效的重要标志。这些数据对于疫苗的设计和疫苗诱导应答的解释具有重要意义。
An understanding of the relationship between the breadth and magnitude of T-cell epitope responses and viral loads is important for the design of effective vaccines. For this study, we screened a cohort of 46 subtype C human immunodeficiency virus type 1 (HIV-1)-infected individuals for T-cell responses against a panel of peptides corresponding to the complete subtype C genome. We used a gamma interferon ELISPOT assay to explore the hypothesis that patterns of T-cell responses across the expressed HIV-1 genome correlate with viral control. The estimated median time from seroconversion to response for the cohort was 13 months, and the order of cumulative T-cell responses against HIV proteins was as follows: Nef > Gag > Pol > Env > Vif > Rev > Vpr > Tat > Vpu. Nef was the most intensely targeted protein, with 97.5% of the epitopes being clustered within 119 amino acids, constituting almost one-third of the responses across the expressed genome. The second most targeted region was p24, comprising 17% of the responses. There was no correlation between viral load and the breadth of responses, but there was a weak positive correlation (r = 0.297; P = 0.034) between viral load and the total magnitude of responses, implying that the magnitude of T-cell recognition did not contribute to viral control. When hierarchical patterns of recognition were correlated with the viral load, preferential targeting of Gag was significantly (r = 0.445; P = 0.0025) associated with viral control. These data suggest that preferential targeting of Gag epitopes, rather than the breadth or magnitude of the response across the genome, may be an important marker of immune efficacy. These data have significance for the design of vaccines and for interpretation of vaccine-induced responses.