Dittmer U, Feldmann G, Sauermann U, Spirng M, Uberla K, Stahl-Hennig C, Hunsmann G
Deutsches Primatenzentrum, Virologie und Immunologie, Göttingen, Germany.
J Gen Virol. 1998 Jul;79 ( Pt 7):1801-7. doi: 10.1099/0022-1317-79-7-1801.
Deletion of the simian immunodeficiency virus (SIV) nef gene leads to an attenuated virus phenotype in vivo. We have previously shown that these viruses induce a potent cellular immune response in macaques. To extend these studies, we established virus-specific short-term T-cell lines from four rhesus macaques infected with a nef deletion mutant of SIV. These T-cell lines proliferated upon restimulation with whole SIV or SIV gp140 antigen in vitro. The proliferating cells were characterized as CD4+ helper T-cells (TH) and their antigen recognition was MHC class II DR-restricted. After antigenic stimulation, they transcribed mRNA for various TH1- and TH2-like cytokines. Using these SIV-specific cell lines, a variety of helper T-cell epitopes in the SIV Env protein were determined with overlapping peptides. TH epitopes were identified throughout the whole SIV Env including both constant and variable regions. Although the recognition of TH epitopes was heterogeneous among different animals, five more broadly reactive T-cell epitopes were identified. As expected, recognition was associated with the MHC class II DRB background of the animals. This is the first report on helper T-cell epitopes in SIV-infected monkeys. Such studies should be of considerable significance for AIDS/ vaccine research.
删除猿猴免疫缺陷病毒（SIV）的nef基因会导致病毒在体内呈现减毒表型。我们之前已经表明，这些病毒能在猕猴体内诱导强烈的细胞免疫反应。为了扩展这些研究，我们从四只感染了SIV nef缺失突变体的恒河猴中建立了病毒特异性短期T细胞系。这些T细胞系在体外经全SIV或SIV gp140抗原再次刺激后会增殖。增殖细胞被鉴定为CD4 +辅助性T细胞（TH），且它们的抗原识别受MHC II类DR限制。抗原刺激后，它们转录了多种TH1和TH2样细胞因子的mRNA。利用这些SIV特异性细胞系，通过重叠肽确定了SIV Env蛋白中的多种辅助性T细胞表位。在整个SIV Env包括恒定区和可变区都鉴定出了TH表位。尽管不同动物对TH表位的识别存在异质性，但还是鉴定出了五个反应性更强泛的T细胞表位。正如预期的那样，识别与动物的MHC II类DRB背景相关。这是关于SIV感染猴子中辅助性T细胞表位的首次报道。此类研究对艾滋病/疫苗研究应具有相当重要的意义。
