In Vivo, Dendritic Cells Can Cross-Present Virus-Like Particles Using an Endosome-to-Cytosol Pathway

• Published in: The Journal of immunology (1950) Vol. 171; no. 5; pp. 2242 - 2250
• Main Authors: Moron, Victor Gabriel, Rueda, Paloma, Sedlik, Christine, Leclerc, Claude
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01-09-2003
• Subjects: Actins - immunology; Actins - metabolism; Amino Acid Sequence; Animals; Antigen Presentation - drug effects; Antigen Presentation - genetics; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - physiology; Brefeldin A; Cell Line; Coated Pits, Cell-Membrane - genetics; Coated Pits, Cell-Membrane - immunology; Coated Pits, Cell-Membrane - virology; Cysteine Endopeptidases - metabolism; Cytosol - immunology; Cytosol - metabolism; Cytosol - virology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; Endopeptidases - metabolism; Endosomes - genetics; Endosomes - immunology; Endosomes - metabolism; Endosomes - virology; Female; Genetic Vectors - administration & dosage; Hybridomas; Hydrogen-Ion Concentration; Hydrolysis; Membrane Microdomains - genetics; Membrane Microdomains - immunology; Membrane Microdomains - virology; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; Multienzyme Complexes - metabolism; Ovalbumin - administration & dosage; Ovalbumin - genetics; Ovalbumin - immunology; Ovalbumin - metabolism; Parvovirus, Porcine - drug effects; Parvovirus, Porcine - genetics; Parvovirus, Porcine - immunology; Parvovirus, Porcine - metabolism; Peptide Fragments - administration & dosage; Peptide Fragments - genetics; Peptide Fragments - immunology; Peptide Fragments - metabolism; Pinocytosis - genetics; Pinocytosis - immunology; Proteasome Endopeptidase Complex; Protein Binding - genetics; Protein Binding - immunology; Signal Transduction - drug effects; Signal Transduction - genetics; Signal Transduction - immunology; Vacuoles - enzymology; Vacuoles - metabolism; Vacuoles - virology; Virion - drug effects; Virion - genetics; Virion - immunology; Virion - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.5.2242

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.