Lucchiari M, Niedermann G, Leipner C, Meyerhans A, Eichmann K, Maier B
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
Int Immunol. 1994 Nov;6(11):1739-49. doi: 10.1093/intimm/6.11.1739.
The immune response of peripheral blood lymphocytes (PBL) of non-exposed human individuals to the Nef protein of HIV-1 was studied. Nef is a regulatory protein of HIV which is immediately expressed after infection and which seems to be important in the pathogenicity of HIV. Nef may therefore serve as a potential target for effective immunity against HIV infection. Epstein-Barr (EBV)-transformed lymphoblastoid B cell lines (LCL) were established from four healthy young seronegative adults and transfected with the Nef gene. These cells served as stimulator cells for autologous PBL in vitro and as target cells for CTL. CTL responses were readily generated against Nef-transfected LCL, consisting of Nef-specific and putative EBV-specific CTL. Nef-specific CTL were generated exclusively from CD8+ cells and were MHC class I restricted. Since a vigorous Nef-specific CTL response in non-infected individuals was unexpected, CTL precursor frequencies were determined by limiting dilution analyses in non-fractionated PBL and in PBL separated into the CD45RO- (naive) and CD45RO+ (memory) T cell populations. As expected, the putative EBV-specific CTL precursors were predominantly found in the CD45RO+ subset at frequencies typical for memory T cells. Nef-specific CTL precursors, in contrast, were found predominantly in the CD45RO- population, at even higher frequencies of approximately 1/1000-1/3000. Nef may thus display either an unusually high number of immunogenic peptides or a limited number of peptides presented in a very efficient way, so that many T cells including low affinity cells, would be triggered.
研究了未接触过HIV的个体外周血淋巴细胞（PBL）对HIV-1 Nef蛋白的免疫反应。Nef是HIV的一种调节蛋白，在感染后立即表达，似乎在HIV的致病性中起重要作用。因此，Nef可能成为有效抵抗HIV感染免疫的潜在靶点。从四名健康的年轻血清阴性成年人中建立了爱泼斯坦-巴尔病毒（EBV）转化的淋巴母细胞样B细胞系（LCL），并用Nef基因进行转染。这些细胞在体外作为自体PBL的刺激细胞以及CTL的靶细胞。针对Nef转染的LCL很容易产生CTL反应，包括Nef特异性和假定的EBV特异性CTL。Nef特异性CTL仅由CD8 +细胞产生，并且受MHC I类限制。由于在未感染个体中出现强烈的Nef特异性CTL反应出乎意料，因此通过有限稀释分析在未分级的PBL以及分离为CD45RO-（幼稚）和CD45RO +（记忆）T细胞群体的PBL中确定CTL前体频率。正如预期的那样，假定的EBV特异性CTL前体主要在CD45RO +亚群中以记忆T细胞典型的频率被发现。相比之下，Nef特异性CTL前体主要在CD45RO-群体中被发现，频率甚至更高，约为1/1000 - 1/3000。因此，Nef可能展示出异常大量的免疫原性肽，或者以非常有效的方式呈现有限数量的肽，从而触发包括低亲和力细胞在内的许多T细胞。
