Dendritic cells transfected with the nef genes of HIV-1 primary isolates specifically activate cytotoxic T lymphocytes from seropositive subjects

The HIV-1 Nef protein down-modulates surface expression of MHC class I prot eins. Primary infected T lymphocytes thus escape lysis by cytotoxic T lymph ocytes (CTL). In contrast, during HIV-1 infection there are strong CTL resp onses to several HIV proteins, and there is mounting evidence that CTL are critical for controlling the virus. The present study was carried out to as sess Nef protein-cell interaction as it occurs in naturally infected antige n-presenting cells. To evaluate the presentation of peptides derived from v iral antigen to CTL, we transfected nef genes obtained from peripheral bloo d mononuclear cells of HIV-1-seropositive subjects into dendritic cells iso lated from monocytes of healthy donors. We demonstrate that expression and subsequent processing of Nef by transfected dendritic cells did not alter t he presentation of an immunodominant epitope of Nef to CTL of HIV+ subjects . However, mutations in nef gene sequences from primary isolates may abolis h this presentation by a mechanism that probably interferes with protein pr ocessing.