HIV-1 Nef impairs MHC class II antigen presentation and surface expression
HIV-1 Nef impairs MHC class II antigen presentation and surface expression
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DOI：
10.1073/pnas.221256498
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发表时间：
2001-10-09
影响因子：
11.1
通讯作者：
Benaroch, P
中科院分区：
文献类型：
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作者：
Stumptner-Cuvelette, P;Morchoisne, S;Benaroch, P
HIV-1感染的细胞可以通过Nef介导的表面MHC 1的下调来避免细胞毒性T淋巴细胞的杀伤。在这里，我们表明，HIV-1 Nef抑制MHC I限制性肽呈递给特定的T细胞，从而可能影响抗病毒免疫反应的诱导。Nef通过降低成熟（即，肽负载的）MHC II，同时增加未成熟的MHC II的水平，未成熟的MHC II由于其与不变链的关联而在功能上不胜任。Nef是唯一具有这种能力的HIV-1基因产物，这在整个HIV-1基因组中也被观察到。内吞途径的其他蛋白质不受Nef表达的影响，这表明Nef对MHC II的影响并不来自内吞途径的一般改变。响应模式，以前的特点是突变的Nef不同的Nef诱导的调制成熟和不成熟的MHC II。此外，观察两种效应所需的Nef剂量明显不同，表明Nef可以通过不同的机制影响MHC II肽呈递。这些机制之间的合作可能使Nef能够有效地抑制MHCII功能。
HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediated down-regulation of surface MHC 1. Here, we show that HIV-1 Nef inhibits MHC I restricted peptide presentation to specific T cells and thus may affect the induction of antiviral immune responses. Nef mediates this effect by reducing the surface level of mature (i.e., peptide-loaded) MHC II while increasing levels of immature MHC II, which are functionally incompetent because of their association with the invariant chain. Nef was the only HIV-1 gene product to possess this capacity, which was also observed in the context of the whole HIV-1 genome. Other proteins of the endocytic pathway were not affected by Nef expression, suggesting that Nef effects on MHC II did not result from a general alteration of the endocytic pathway. Response patterns to previously characterized mutations of Nef differed for Nef-induced modulation of mature and immature MHC II. Furthermore, the doses of Nef required to observe each of the two effects were clearly different, suggesting that Nef could affect MHC II peptide presentation through distinct mechanisms. Cooperation between those mechanisms may enable Nef to efficiently inhibit MHC II function.