EA4271 Laboratoire d'Immunovirologie et Polymorphisme Génétique, Université de Nantes, Nantes, France.
J Clin Immunol. 2011 Aug;31(4):681-9. doi: 10.1007/s10875-011-9520-z. Epub 2011 Apr 14.
Many drug-resistance mutations in HIV-1 reverse transcriptase fall within cytotoxic T lymphocytes (CTL) epitopes, but studies of the response to these epitopes in patients with virological failure are lacking. We therefore compared IFN-γ ELISPOT responses to the YV9 epitope (RT181-189) covering the lamivudine resistance mutation, M184V, in HLA-A2(+) antiretroviral treatment (ART)-naive patients (n = 19), to those found in HLA-A2(+) patients with virological failure (n = 15). Ten ART-naive patients had an ELISPOT response to the wild-type epitope that cross-reacted with the mutant epitope. Two patients with virological failure showed a specific response to the 184V mutant epitope. Responses against YV9 were strongly associated (p = 0.005) with the presence of a 177E mutation, and the same tendency was observed in an independent cohort of patients (n = 22). These results indicate that variants in flanking residues may influence CTL responses to conserved subdominant HIV-1 epitopes.
许多 HIV-1 逆转录酶的耐药突变位于细胞毒性 T 淋巴细胞（CTL）表位内，但缺乏对这些表位在病毒学失败患者中的反应的研究。因此，我们比较了 HLA-A2(+)抗逆转录病毒治疗（ART）初治患者（n=19）和病毒学失败患者（n=15）中 YV9 表位（RT181-189）的 IFN-γ ELISPOT 反应，该表位涵盖了拉米夫定耐药突变 M184V。10 名 ART 初治患者对与突变表位发生交叉反应的野生型表位产生了 ELISPOT 反应。2 名病毒学失败患者对 184V 突变表位表现出特异性反应。针对 YV9 的反应与 177E 突变的存在强烈相关（p=0.005），在另一组独立的患者中也观察到了同样的趋势（n=22）。这些结果表明，侧翼残基的变异可能影响对保守的次要 HIV-1 表位的 CTL 反应。
