title: Early phagosomes in dendritic cells form a cellular compartment sufficient for cross presentation of exogenous antigens.
abstract: Conventionally, MHC class I-restricted antigen (Ag) processing requires the action of the multimolecular peptide-loading complex within the endoplasmic reticulum (ER). Here we show that early phagosomes from human dendritic cells (DCs) contain the peptide-loading complex, incorporating MHC class I, beta2 microglobulin, transporter associated with Ag processing (TAP), calreticulin, tapasin, and ERp57. Antigenic peptides could be translocated into purified phagosomes by TAP and loaded onto cognate class I molecules, inducing their specific dissociation from the loading complex. Endoglycosidase H-sensitive class I molecules were detected at the DC cell surface, suggesting that these molecules traffic there directly from phagosomes. Macropinocytosis also allowed internalized soluble Ags access to an ER-like compartment containing the class I loading complex. Blockade of TAP by endocytosis of a soluble derivative of human cytomegalovirus protein US6 confirmed that, although retrotranslocation into the cytosol is critical for processing, efficient association of class I molecules with peptides derived from exogenous Ags occurs within a compartment directly accessible to internalized proteins. Together, this evidence suggests that early phagosomes and pinosomes facilitate cross presentation of exogenous Ags by DCs.
authors.affiliation: Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Ackerman
authors.forename: Christoph
authors.initials: C
authors.lastname: Kyritsis
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
authors.forename: Peter
authors.initials: P
authors.lastname: Cresswell
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D002352:Carrier Proteins; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D007700:Kinetics; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D010588:Phagosomes / Q000276:immunology* / Q000502:physiology; D010873:Pinocytosis; D021381:Protein Transport; D011951:Receptors, Complement / Q000276:immunology / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000276:immunology / Q000378:metabolism
chemical_list: C087299:C1QBP protein, human; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D001613:beta 2-Microglobulin; C032402:complement 1q receptor