Transporter-independent processing of HIV-1 envelope protein for recognition by CD8⁺ T cells

CDS⁺ 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 cells^1-4. Processing begins in the cytosol^5-7 with the generation of peptides, possibly by a protease complex with MHC-encoded subunits, known as the proteasome^8-11. Transport of the resulting cytosolic peptides into the endoplasmic 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 is 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 cells by a novel Tap-l/Tap-2-independent pathway that seems to be localized to the endoplasmic reticulum.