A Phagosome-to-cytosol Pathway for Exogenous Antigens Presented on MHC Class I Molecules

Peptides from endogenous proteins are presented by major histocompatibility complex class I molecules, but antigens (Ags) in the extracellular fluids are generally not. However, pathogens or particulate Ags that are internalized into phagosomes of macrophages (M phi s) stimulate CD8 T cells. The presentation of these Ags is resistant to chloroquine but is blocked by inhibitors of the proteasome, a mutation in the TAP1-TAP2 transporter, and brefeldin A. Moreover, phagocytosis of a ribosomal-inactivating protein inhibited M phi protein synthesis. These results demonstrate that M phi s transfer Ags from phagosomes into the cytosol and that endogenous and exogenous Ags use a final common pathway for class I presentation.