Multiple effector functions mediated by human immunodeficiency virus-specific CD4+ T-cell clones
Multiple effector functions mediated by human immunodeficiency virus-specific CD4+ T-cell clones
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DOI：
10.1128/jvi.75.20.9771-9779.2001
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发表时间：
2001-10-01
影响因子：
5.4
通讯作者：
Rosenberg, ES
中科院分区：
文献类型：
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作者：
Norris, PJ;Sumaroka, M;Rosenberg, ES
越来越多的证据表明，人类免疫缺陷病毒1型（HIV-1）的GAG特异性T辅助细胞有助于有效的抗病毒控制，但其功能特征和这种反应所针对的精确表位仍有待确定。在这项研究中，我们从HIV-1感染者中产生了对Gag特异的CD 4（+）T细胞克隆，这些HIV-1感染者的外周血单核细胞中可检测到强烈的Gag特异性反应。鉴定了含有T辅助表位的多个肽，包括Gag的亲环蛋白结合结构域中的最小肽VHAGPIAG（氨基酸218至226）。肽识别所有克隆检查诱导细胞增殖，γ干扰素（IFN-γ）的分泌，和细胞溶解活性。Concanamycin A和EGTA可抑制细胞溶解，但布雷菲德菌素A或抗Fas抗体不能抑制细胞溶解，这意味着穿孔素介导的细胞溶解机制。此外，丝氨酸酯酶释放到细胞外介质中，细胞溶解颗粒的标志物，被证明在抗原特异性，剂量依赖性的方式。这些数据表明，T辅助细胞可以靶向p24 Gag蛋白的多个区域，并表明细胞溶解活性可能是这些细胞的抗病毒作用的一个组成部分。
Mounting evidence suggests that human immunodeficiency virus type 1 (HIV-1) Gag-specific T helper cells contribute to effective antiviral control, but their functional characteristics and the precise epitopes targeted by this response remain to be defined. In this study, we generated CD4(+) T-cell clones specific for Gag from HIV-1-infected persons with vigorous Gag-specific responses detectable in peripheral blood mononuclear cells. Multiple peptides containing T helper epitopes were identified, including a minimal peptide, VHAGPIAG (amino acids 218 to 226), in the cyclophilin binding domain of Gag. Peptide recognition by all clones examined induced cell proliferation, gamma interferon (IFN-gamma) secretion, and cytolytic activity. Cytolysis was abrogated by concanamycin A and EGTA but not brefeldin A or anti-Fas antibody, implying a perforin-mediated mechanism of cell lysis. Additionally, serine esterase release into the extracellular medium, a marker for cytolytic granules, was demonstrated in an antigen-specific, dose-dependent fashion. These data indicate that T helper cells can target multiple regions of the p24 Gag protein and suggest that cytolytic activity may be a component of the antiviral effect of these cells.