HIV-1 Nef impairs MHC class II antigen presentation and surface expression

HIV-1-infected cells can avoid cytotoxic T lymphocyte killing by Nef-mediat ed 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 affe ct the induction of antiviral immune responses. Nef mediates this effect by reducing the surface level of mature (i.e., peptide-loaded) MHC II while i ncreasing levels of immature MHC II, which are functionally incompetent bec ause 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 conte xt 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 n ot result from a general alteration of the endocytic pathway. Response patt erns to previously characterized mutations of Nef differed for Nef-induced modulation of mature and immature MHC II. Furthermore, the doses of Nef req uired to observe each of the two effects were clearly different, suggesting that Nef could affect MHC II peptide presentation through distinct mechani sms. Cooperation between those mechanisms may enable Nef to efficiently inh ibit MHC II function.