Downregulation of major histocompatibility class I on human dendritic cells by HIV Nef impairs antigen presentation to HIV-specific CD8(+) T lymphocytes

The HIV early regulatory Nef protein downregulates surface expression of ma jor histocompatibility class I (MHC I) molecules on various immortalized ce ll lines and on T lymphocytes. MHC I-restricted presentation induces CD8(+) T cell responses, which have a major role in limiting HIV infection. Induc tion of primary immune responses requires dendritic cells, which are major candidates as the first cells that can internalize the virus and present it to T cells in mucosal contamination. To test the effect of Nef on MHC I-re stricted antigen presentation by dendritic cells, we used recombinant vacci nia viruses. Flow cytometric analysis of double labeling for a vaccinia pro tein and MHC I showed that HIV-1 Lai Nef indeed downregulated MHC I surface expression on dendritic cells. MHC I-restricted presentation to a Nef-spec ific CD8(+) cell clone from an infected patient was decreased in an interfe ron gamma ELISpot assay. Presentation of a reverse transcriptase epitopic p eptide on sorted Nef-infected cells was decreased in a peptide concentratio n-dependent way, confirming the role of MHC I downregulation in the impairm ent of the CD8(+) cell-specific response. Therefore, Nef downregulates MHC I surface expression on human dendritic cells, impairing presentation to HI V-specific CD8(+) cells. This action of Nef probably induces a deleterious delay in the early CD8(+) responses during the first days of infection and at the onset of new viral mutants.