Abstract
Major histocompatibility complex (MHC) class I cross-presentation is thought to involve two pathways, one of which depends on both the TAP transporters and the proteasome and the other on neither. We found that preincubation of TAP-deficient dendritic cells at low temperature increases the density of MHC class I at the surface and fully restores cross-presentation of phagocytosed antigen, but not of soluble antigen internalized through receptors. Restoration of cross-presentation by TAP-deficient cells requires antigen degradation by the proteasome. Thus, TAP might mainly be required for recycling cell surface class I molecules during cross-presentation of phagocytosed antigens. Furthermore, phagosomes-but not endosomes-seem to have a TAP-independent mechanism to import peptides generated by cytosolic proteasome complexes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / metabolism
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Animals
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Antigen Presentation / drug effects
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Antigen Presentation / immunology*
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Antigens / immunology*
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Cross-Priming / drug effects
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Cross-Priming / immunology*
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Endocytosis / drug effects
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Endocytosis / immunology
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Histocompatibility Antigens Class I / immunology
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Mice
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Models, Immunological
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Phagocytosis / drug effects
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Phagocytosis / immunology*
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Protease Inhibitors / pharmacology
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Proteasome Endopeptidase Complex / metabolism*
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Receptors, Immunologic / metabolism
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Signal Transduction / drug effects
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Signal Transduction / immunology*
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Solubility / drug effects
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Temperature
Substances
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ATP-Binding Cassette Transporters
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Antigens
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Histocompatibility Antigens Class I
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Protease Inhibitors
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Receptors, Immunologic
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transporter associated with antigen processing (TAP)
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Proteasome Endopeptidase Complex