Abstract
Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC class I Ag presentation. Our findings provide the first evidence for a connection between DC maturation, MHC class I-restricted Ag presentation, and DALIS formation, which is further supported by the observation that DALIS contain ubiquitinated influenza nucleoprotein.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / immunology*
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Antigen-Presenting Cells / virology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / virology
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Cell Differentiation / immunology
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Cell Line
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Cell Line, Tumor
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Cells, Cultured
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Cytoplasmic Structures / immunology*
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Cytoplasmic Structures / metabolism
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Cytoplasmic Structures / virology*
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Dendritic Cells / cytology*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / virology
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Epitopes, T-Lymphocyte / biosynthesis
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / metabolism
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Humans
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Influenza A virus / immunology*
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Mice
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Nucleocapsid Proteins
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Nucleoproteins / biosynthesis
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Nucleoproteins / genetics
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Nucleoproteins / metabolism
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RNA-Binding Proteins / biosynthesis
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Receptors, Immunologic / physiology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / virology
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Time Factors
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Ubiquitin / metabolism
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Viral Core Proteins / biosynthesis
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Viral Core Proteins / genetics
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Viral Core Proteins / metabolism
Substances
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Epitopes, T-Lymphocyte
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NP protein, Influenza A virus
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Nucleocapsid Proteins
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Nucleoproteins
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RNA-Binding Proteins
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Receptors, Immunologic
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Tlr2 protein, mouse
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Tlr4 protein, mouse
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Ubiquitin
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Viral Core Proteins