Collins K L, Chen B K, Kalams S A, Walker B D, Baltimore D
Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nature. 1998 Jan 22;391(6665):397-401. doi: 10.1038/34929.
Cytotoxic T lymphocytes (CTLs) lyse virally infected cells that display viral peptide epitopes in association with major histocompatibility complex (MHC) class I molecules on the cell surface. However, despite a strong CTL response directed against viral epitopes, untreated people infected with the human immunodeficiency virus (HIV-1) develop AIDS. To resolve this enigma, we have examined the ability of CTLs to recognize and kill infected primary T lymphocytes. We found that CTLs inefficiently lysed primary cells infected with HIV-1 if the viral nef gene product was expressed. Resistance of infected cells to CTL killing correlated with nef-mediated downregulation of MHC class I and could be overcome by adding an excess of the relevant HIV-1 epitope as soluble peptide. Thus, Nef protected infected cells by reducing the epitope density on their surface. This effect of nef may allow evasion of CTL lysis by HIV-1-infected cells.
细胞毒性T淋巴细胞（CTLs）可裂解在细胞表面与主要组织相容性复合体（MHC）I类分子结合展示病毒肽表位的病毒感染细胞。然而，尽管针对病毒表位有强烈的CTL反应，但未接受治疗的人类免疫缺陷病毒（HIV-1）感染者仍会发展为艾滋病。为了解决这一谜团，我们检测了CTL识别并杀死感染的原代T淋巴细胞的能力。我们发现，如果病毒nef基因产物表达，CTL对感染HIV-1的原代细胞的裂解效率低下。感染细胞对CTL杀伤的抗性与nef介导的MHC I类分子下调相关，并且可以通过添加过量的相关HIV-1表位作为可溶性肽来克服。因此，Nef通过降低感染细胞表面的表位密度来保护它们。nef的这种作用可能使HIV-1感染的细胞逃避CTL裂解。
