Achour A, Picard O, Zagury D, Sarin P S, Gallo R C, Naylor P H, Goldstein A L
Universite Pierre et Marie Curie, Unité Enseignement et Recherche, Paris, France.
Proc Natl Acad Sci U S A. 1990 Sep;87(18):7045-9. doi: 10.1073/pnas.87.18.7045.
Evaluation of the immune response of individuals exposed to human immunodeficiency virus (HIV) is an important component of any plan designed to lead toward the development of an AIDS vaccine. Since the levels of antibodies to HIV p17 and the synthetic p17 peptide HGP-30 correlate with stages of progression to AIDS, studies were initiated to determine whether cytotoxic lymphocytes directed toward target cells pulsed with HGP-30 and radioactive chromium were present in seropositive individuals. The significance of such cells in controlling HIV viral infection has recently been enhanced by reports that HIV p17 is on the surface of infected cells and that an inactivated virus vaccine depleted of viral envelope appears to be effective in controlling expression. The selection of HGP-30 as the p17 peptide to be evaluated in early studies is based on the presence of both T-cell and B-cell epitopes as predicted by computer modeling and mouse studies and the demonstration of in vitro neutralization activity by antibodies to the epitope. By using B-lymphoblastoid cells pulsed with HGP-30 and radioactive chromium as autologous targets and mixed leukocyte culture-expanded peripheral blood lymphocytes as effectors, CD8+ cytotoxic T lymphocytes against HGP-30-coated targets were identified in seropositive individuals. In this report we demonstrate that a synthetic p17 epitope can be a target for major histocompatibility complex-restricted cytotoxic T lymphocytes in HIV-infected individuals.
评估暴露于人类免疫缺陷病毒(HIV)个体的免疫反应,是任何旨在研发艾滋病疫苗计划的重要组成部分。由于针对HIV p17及合成p17肽HGP-30的抗体水平与艾滋病进展阶段相关,因此开展了研究以确定血清反应阳性个体中是否存在针对用HGP-30和放射性铬脉冲处理的靶细胞的细胞毒性淋巴细胞。近期有报道称HIV p17存在于受感染细胞表面,且一种去除病毒包膜的灭活病毒疫苗似乎在控制表达方面有效,这增强了此类细胞在控制HIV病毒感染中的重要性。早期研究中选择HGP-30作为待评估的p17肽,是基于计算机建模和小鼠研究预测其同时存在T细胞和B细胞表位,以及针对该表位的抗体具有体外中和活性的证明。通过使用用HGP-30和放射性铬脉冲处理的B淋巴母细胞作为自体靶细胞,以及混合白细胞培养扩增的外周血淋巴细胞作为效应细胞,在血清反应阳性个体中鉴定出了针对包被HGP-30的靶细胞的CD8 +细胞毒性T淋巴细胞。在本报告中,我们证明合成的p17表位可以成为HIV感染个体中主要组织相容性复合体限制的细胞毒性T淋巴细胞的靶标。