TRANSPORTER-INDEPENDENT PROCESSING OF HIV-1 ENVELOPE PROTEIN FOR RECOGNITION BY CD8-CELLS( T)

CD8+ cytolytic T lymphocytes (CTL) identify virally infected cells by recognizing processed viral antigen in association with class I major histocompatibility complex (MHC) molecules on infected cells1-4. Proce ssing begins in the cytosol5-7 with the generation of peptides, possib ly by a protease complex with MHC-encoded subunits, known as the prote asome8-11. Transport of the resulting cytosolic peptides into the endo plasmic reticulum for association with class I molecules is essential and probably involves a heterodimer of the MHC-encoded proteins, Tap-1 and Tap-2(12-17). The site of processing of viral envelope proteins i s uncertain. These proteins are not present in the cytosol because of cotranslational translocation into the endoplasmic reticulum. We show here that the HIV-1 envelope (env) protein is processed in infected ce lls by a novel Tap-1/Tap-2-independent pathway that seems to be locali zed to the endoplasmic reticulum.