Haas G, Samri A, Gomard E, Hosmalin A, Duntze J, Bouley J M, Ihlenfeldt H G, Katlama C, Autran B
Department of Molecular Biology, Max-Planck-Institut für Infektionsbiologie, Berlin, Germany.
AIDS. 1998 Aug 20;12(12):1427-36. doi: 10.1097/00002030-199812000-00004.
To determine immunodominant regions and new epitopes for cytotoxic T cells (CTL) directed against the HIV-1 pol products reverse transcriptase (RT), integrase and protease in a large cohort of patients at different stages of disease.
Cross-sectional analysis of 98 patients from the French IMMUNOCO cohort (CD4 counts: 125-1050 x 10(6) cells/l), monitored for CTL recognition of HIV-1 pol products using recombinant vaccinia virus constructs and synthetic peptides.
Memory CTL responses against HIV-1 pol products were detected in 78% of all patients whatever the stage of disease. RT was more immunogenic (81%, 30 out of 37 patients) than integrase and protease (51% and 24%, respectively). CTL recognition of RT was more frequent against Pol amino acids 310-460 (61%, 11 out of 18 patients) than against the other three portions (Pol 168-310, Pol 450-600, Pol 590-728) in patients with CD4 counts > 400 x 10(6)/l, whereas in patients at advanced stages no prominent differences were observed. Two new clusters of antigenic regions were found in the NH2 segment: three epitopes between amino-acids Pol 200 and 217 and four epitopes between amino-acids Pol 346 and 387, using five different HLA-restricting elements. A new cluster of three conserved epitopes was found in the COOH segment of RT.
This study shows that memory CTL responses against HIV-1 RT, integrase and protease are detectable in most patients at different stages of disease. The capacity of CTL to recognize simultaneously clusters of epitopes may become important for the immune control to reinforce antiretroviral drug efficiency.
在一大群处于不同疾病阶段的患者中，确定针对HIV-1 pol产物逆转录酶（RT）、整合酶和蛋白酶的细胞毒性T细胞（CTL）的免疫显性区域和新表位。
对来自法国IMMUNOCO队列的98名患者（CD4计数：125 - 1050×10⁶个细胞/升）进行横断面分析，使用重组痘苗病毒构建体和合成肽监测CTL对HIV-1 pol产物的识别。
无论疾病处于何种阶段，78%的患者检测到针对HIV-1 pol产物的记忆CTL反应。RT比整合酶和蛋白酶更具免疫原性（分别为81%，37名患者中的30名；51%和24%）。在CD4计数>400×10⁶/升的患者中，CTL对RT的识别在Pol氨基酸310 - 460区域（61%，18名患者中的11名）比在其他三个区域（Pol 168 - 310、Pol 450 - 600、Pol 590 - 728）更频繁，而在疾病晚期患者中未观察到显著差异。在NH₂段发现了两个新的抗原区域簇：使用五种不同的HLA限制元件，在氨基酸Pol 200和217之间有三个表位，在氨基酸Pol 346和387之间有四个表位。在RT的COOH段发现了一个由三个保守表位组成的新簇。
本研究表明，在大多数处于不同疾病阶段的患者中可检测到针对HIV-1 RT、整合酶和蛋白酶的记忆CTL反应。CTL同时识别表位簇的能力对于加强抗逆转录病毒药物疗效的免疫控制可能变得很重要。
