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Dendritic Cell Aggresome-Like-Induced Structure Formation and Delayed Antigen Presentation Coincide in Influenza Virus-Infected Dendritic Cells¹

Sylvia Herter^*,, Philipp Osterloh^*, Norbert Hilf, Gerd Rechtsteiner^*, Jörg Höhfeld, Hans-Georg Rammensee and Hansjörg Schild^2,*,

^* Institute for Immunology, University of Mainz, Mainz, Germany; Institute for Cell Biology, Department of Immunology, Eberhard-Karls University, Tübingen, Germany; and Institute for Cell Biology, Rheinische Friedrich-Wilhelms University, Bonn, Germany

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.

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