Koenig S, Earl P, Powell D, Pantaleo G, Merli S, Moss B, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1988 Nov;85(22):8638-42. doi: 10.1073/pnas.85.22.8638.
Freshly separated unfractionated peripheral blood mononuclear cells (PBMC) and cloned cell lines from a healthy human immunodeficiency virus 1 (HIV-1)-seropositive individual were examined for cytotoxic responses to HIV proteins expressed by recombinant vaccinia viruses. It was found that freshly isolated PBMC recognize variant envelope proteins of HIV-1 but not a more distantly related envelope protein derived from the simian immunodeficiency virus (SIVmac). Although the effector cells were predominantly CD8+, both MHC-matched and -unmatched target cells were lysed. Cytotoxic T lymphocyte (CTL) clones were found to lyse cells expressing HIV-1 envelope or reverse transcriptase. In contrast to the cytotoxic response detected with PBMC, the cloned CTLs were major histocompatibility complex (MHC) class I restricted. Our finding that a cloned CTL line lysed cells expressing highly divergent HIV envelopes strongly suggested that a conserved epitope was recognized. Identification of these shared epitopes may assist in designing a vaccine for HIV-1 that could stimulate MHC-restricted cytotoxic responses.
对从一名健康的人类免疫缺陷病毒1型(HIV-1)血清反应阳性个体新鲜分离的未分级外周血单个核细胞(PBMC)和克隆细胞系进行检测,观察其对重组痘苗病毒表达的HIV蛋白的细胞毒性反应。结果发现,新鲜分离的PBMC能识别HIV-1的变异包膜蛋白,但不能识别来自猿猴免疫缺陷病毒(SIVmac)的亲缘关系更远的包膜蛋白。尽管效应细胞主要为CD8+,但MHC匹配和不匹配的靶细胞均被裂解。发现细胞毒性T淋巴细胞(CTL)克隆可裂解表达HIV-1包膜或逆转录酶的细胞。与PBMC检测到的细胞毒性反应不同,克隆的CTL受主要组织相容性复合体(MHC)I类分子限制。我们发现一个克隆的CTL系可裂解表达高度不同的HIV包膜的细胞,这强烈提示存在一个保守表位被识别。鉴定这些共同表位可能有助于设计一种可刺激MHC限制的细胞毒性反应的HIV-1疫苗。