Haas G, Plikat U, Debré P, Lucchiari M, Katlama C, Dudoit Y, Bonduelle O, Bauer M, Ihlenfeldt H G, Jung G, Maier B, Meyerhans A, Autran B
Laboratory of Cellular and Tissue Immunology, Hospital Pitié-Salpétriére, Paris, France.
J Immunol. 1996 Nov 1;157(9):4212-21.
The vigorous CTL response directed against HIV is considered to be important in reducing HIV viral load, although it is unable to stop ongoing viral replication, which generates new antigenic variants. We analyzed the impact of sequential changes in five epitopes of HIV-1 Nef on CTL recognition in four stable patients. A high rate of variation was found, and in all these patients we could detect CTL specific for 32 out of 36 autologous viral variants occurring in 5 HLA-A2- or HLA-B7-restricted Nef epitopes at two time points. Two distinct patterns for dynamics of CTL responses to viral variation were observed: 1) temporary amplification of viral variants followed by expansion of variant-specific CTL, ultimately leading to the disappearance of 12 out of the 14 initial epitope variants within two years. A second set of viral variants that had replaced the initial ones could also stimulate specific CTL precursors in the context of the same or an alternative HLA molecule; and 2) persistence of 2 viral variants in relatively conserved epitopes despite specific CTL recognition. Therefore, a remarkable flexibility of the immune system allows constant adaptation of CTL to multiple HIV variants and thus elimination of HIV variant-producing cells in slow progressors.
针对HIV的强烈细胞毒性T淋巴细胞（CTL）反应被认为在降低HIV病毒载量方面很重要，尽管它无法阻止正在进行的病毒复制，而这种复制会产生新的抗原变体。我们分析了HIV-1 Nef的五个表位的序列变化对四名病情稳定患者的CTL识别的影响。发现变异率很高，并且在所有这些患者中，我们能够在两个时间点检测到针对5个HLA-A2或HLA-B7限制性Nef表位中出现的36种自体病毒变体中的32种的CTL。观察到CTL对病毒变异反应的两种不同模式：1）病毒变体的暂时扩增，随后是变体特异性CTL的扩增，最终导致14种初始表位变体中的12种在两年内消失。取代初始变体的第二组病毒变体也可以在相同或替代的HLA分子的背景下刺激特定的CTL前体；2）尽管有特异性CTL识别，但相对保守表位中的2种病毒变体持续存在。因此，免疫系统的显著灵活性使CTL能够不断适应多种HIV变体，从而在病情进展缓慢的患者中消除产生HIV变体的细胞。
