Science · 1995 · 872 citations · 21 references
Life SciencesCell BiologyImmunologyCellular ImmunologyInflammationInnate ImmunityAntigen PresentationAntigen ProcessingHistocompatibility AntigensMacrophage BiologyMajor Histocompatibility ComplexPhagocyte BiologyAntigen Presentation By MacrophagesCd8 Positive T CellsCd8 T Cell ActivationMacrophage Antigen PresentationMacrophage Antigen ProcessingMajor Histocompatibility Complex Class I PresentationMajor Histocompatibility Complex Class I RecognitionMhc Class I Molecules
Endogenous peptides are presented by MHC class I, whereas extracellular antigens are typically not. Macrophage phagocytosis of pathogens or particulate antigens activates CD8 T cells. Antigen presentation from phagosomes is chloroquine‑resistant but blocked by proteasome inhibitors, TAP1‑TAP2 mutation, and brefeldin A, and phagocytosis of a ribosomal‑inactivating protein suppresses macrophage protein synthesis, demonstrating that macrophages shuttle antigens into the cytosol and that endogenous and exogenous antigens share a common MHC class I pathway.
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 (MØs) 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 MØ protein synthesis. These results demonstrate that MØs transfer Ags from phagosomes into the cytosol and that endogenous and exogenous Ags use a final common pathway for class I presentation.
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Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor Antigens
Alex Y. Huang, Paul T. Golumbek, Mojgan Ahmadzadeh et al. · Science · 1994 · 1.2K citations
Life Sciences, Immunology, Oncology +17