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.
Kovacsovics-Bankowski
M
M
Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, MA 02115.
Rock
K L
KL
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism*; D020126:Brefeldin A; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D009842:Oligopeptides / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D054789:Ribosome Inactivating Proteins, Type 1
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D003517:Cyclopentanes; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D009842:Oligopeptides; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human; D020126:Brefeldin A; C025674:GEL protein, Gelonium multiflorum; D002738:Chloroquine; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex