In vivo, dendritic cells can cross-present virus-like particles using an endosome-to-cytosol pathway.
Recombinant parvovirus-like particles (PPV-VLPs) are particulate exogenous Ags that induce strong CTL response in the absence of adjuvant. In the present report to decipher the mechanisms responsible for CTL activation by such exogenous Ag, we analyzed ex vivo and in vitro the mechanisms of capture and processing of PPV-VLPs by dendritic cells (DCs). In vivo, PPV-VLPs are very efficiently captured by CD8alpha- and CD8alpha+ DCs and then localize in late endosomes of DCs. Macropinocytosis and lipid rafts participate in PPV-VLPs capture. Processing of PPV-VLPs does not depend upon recycling of MHC class I molecules, but requires vacuolar acidification as well as proteasome activity, TAP translocation, and neosynthesis of MHC class I molecules. This study therefore shows that in vivo DCs can cross-present PPV-VLPs using an endosome-to-cytosol processing pathway.
Morón
Víctor Gabriel
VG
Unité de Biologie des Régulations Immunitaires, Institut National de la Santé et de la Recherche Médicale, E352, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Rueda
Paloma
P
Sedlik
Christine
C
Leclerc
Claude
C
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000199:Actins / Q000276:immunology / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics; D020126:Brefeldin A; D002460:Cell Line; D003034:Coated Pits, Cell-Membrane / Q000235:genetics / Q000276:immunology / Q000821:virology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003600:Cytosol / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D010450:Endopeptidases / Q000378:metabolism; D011992:Endosomes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D006825:Hybridomas; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D021962:Membrane Microdomains / Q000235:genetics / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D028323:Parvovirus, Porcine / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010873:Pinocytosis / Q000235:genetics / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014617:Vacuoles / Q000201:enzymology / Q000378:metabolism / Q000821:virology; D014771:Virion / Q000187:drug effects / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D000199:Actins; D009097:Multienzyme Complexes; C110366:OVA-8; D010446:Peptide Fragments; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; D020126:Brefeldin A; D010047:Ovalbumin; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex