A proteasome-dependent, TAP-independent pathway for cross-presentation of phagocytosed antigen.
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.
Institut National de la Santé et de la Recherché Médicale, Unité 1013, Paris 75015, France.
Nawel
N
Merzougui
Roland
R
Kratzer
Loredana
L
Saveanu
Peter
P
van Endert
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D045142:Cross-Priming / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D012995:Solubility / Q000187:drug effects; D013696:Temperature
D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D015395:Histocompatibility Antigens Class I; D011480:Protease Inhibitors; D011971:Receptors, Immunologic; C477327:transporter associated with antigen processing (TAP); D046988:Proteasome Endopeptidase Complex