Nehete P N, Lewis D E, Tang D N, Pollack M S, Sastry K J
Department of Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Bastrop 78602, USA.
Viral Immunol. 1998;11(3):119-29. doi: 10.1089/vim.1998.11.119.
Approximately 5% of people with human immunodeficiency virus type 1 (HIV-1) infection remain free of disease for 10 or more years. These long-term nonprogressors (LTNPs) exhibit lower viral loads and stable CD4+ lymphocyte counts. The immunologic basis for this disease-free condition is not known. Because cytotoxic T lymphocytes (CTLs) constitute a major immune defense mechanism for sustained recovery from viral infections, we analyzed HIV-specific CTL responses in three asymptomatic LTNPs. We observed the presence of HIV-1 envelope-specific CTL responses mediated by HLA class I C-restricted CD8+ cells in these individuals. Using autologous target cells and a panel of HLA-matching and -mismatching B-cell lines as targets, we determined that HLA-Cw7 is the restricting element for the observed CTL activity. Additionally, we identified three peptides, one previously not reported, from conserved regions in the envelope protein as CTL epitopes. We previously reported these peptides to be efficient in inducing HIV-specific cellular immune responses in murine and nonhuman primate models. Our results support the role of the HLA-C locus in generating CTL responses and constitute the first report of an HLA-Cw7-restricted HIV-1 envelope-specific CTL response in HIV+ LTNPs, which may be important in the control of HIV replication in vivo.
约5%的1型人类免疫缺陷病毒（HIV-1）感染者可在10年或更长时间内保持无病状态。这些长期不进展者（LTNP）的病毒载量较低，CD4+淋巴细胞计数稳定。这种无病状态的免疫基础尚不清楚。由于细胞毒性T淋巴细胞（CTL）是病毒感染持续恢复的主要免疫防御机制，我们分析了3名无症状LTNP的HIV特异性CTL反应。我们观察到这些个体中存在由HLA I类C限制性CD8+细胞介导的HIV-1包膜特异性CTL反应。使用自体靶细胞和一组HLA匹配及不匹配的B细胞系作为靶标，我们确定HLA-Cw7是观察到的CTL活性的限制元件。此外，我们从包膜蛋白的保守区域鉴定出3种肽作为CTL表位，其中一种以前未报道过。我们之前报道过这些肽在小鼠和非人类灵长类动物模型中能有效诱导HIV特异性细胞免疫反应。我们的结果支持HLA-C基因座在产生CTL反应中的作用，并构成了HIV+ LTNP中HLA-Cw7限制性HIV-1包膜特异性CTL反应的首次报道，这可能对体内HIV复制的控制很重要。
