title: Receptor-mediated phagocytosis elicits cross-presentation in nonprofessional antigen-presenting cells.
abstract: In cross-presentation by dendritic cells (DCs), internalized proteins are retrotranslocated into the cytosol, degraded by the proteasome, and the generated antigenic peptides bind to MHC class I molecules for presentation on the cell surface. Endoplasmic reticulum (ER) contribution to phagosomal membranes is thought to provide antigen access to the ER-associated degradation (ERAD) machinery, allowing cytosolic dislocation. Because the ERAD pathway is present in all cell types and exogenous antigens encounter an ER-containing compartment during phagocytosis, we postulated that forcing phagocytosis in cell types other than DCs would render them competent for cross-presentation. Indeed, FcRgammaIIA expression endowed 293T cells with the capacity for both phagocytosis and ERAD-mediated cross-presentation of an antigen provided as an immune complex. The acquisition of this ability by nonprofessional antigen-presenting cells suggests that a function potentially available in all cell types has been adapted by DCs for presentation of exogenous antigens by MHC class I molecules.
authors.affiliation: Howard Hughes Medical Institute, Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, P.O. Box 208011, New Haven, CT 06520-8011, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Giodini
authors.forename: Christoph
authors.initials: C
authors.lastname: Rahner
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D000906:Antibodies / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000648:ultrastructure; D037281:Calnexin / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D010587:Phagocytosis / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D000906:Antibodies; D017452:Receptors, IgG; D037281:Calnexin