SURROGATE ANTIGEN-PROCESSING MEDIATED BY TAP-DEPENDENT ANTIGENIC PEPTIDE SECRETION

MHC class I proteins assemble with peptides in the ER. The peptides ar e predominantly generated from cytoplasmic proteins, probably by the a ction of the proteasome, a multicatalytic proteinase complex. Peptides are translocated into the ER by the transporters associated with anti gen processing (TAP), and bind to the MHC class I molecules before tra nsport to the cell surface. Here, we use a new functional assay to dem onstrate that peptides derived from vesicular stomatitis virus nucleop rotein (VSV-N) antigen are actively secreted from cells. This secretio n pathway is dependent on the expression of TAP transporters, but is i ndependent of the MHC genotype of the donor cells. Furthermore, the ex pression and transport of MHC class I molecules is not required. This novel pathway is sensitive to the protein secretion inhibitors brefeld in A (BFA) and a temperature block at 21 degrees C, and is also inhibi ted by the metabolic poison, azide, and the protein synthesis inhibito r, emetine. These data support the existence of a novel form of peptid e secretion that uses the TAP transporters, as opposed to the ER trans locon, to gain access to the secretion pathway. Finally, we suggest th at this release of peptides in the vicinity of uninfected cells, which we term surrogate antigen processing, could contribute to various imm une and secretory phenomena.