The maturation of murine dendritic cells induced by human adenovirus is mediated by the fiber knob domain.
We investigated the mechanism of adenovirus serotype 5 (Ad5)-mediated maturation of bone marrow-derived murine dendritic cells (DC) using (i) Ad5 vectors with wild-type capsid (AdE1 degrees, AdGFP); (ii) Ad5 vector mutant deleted of the fiber C-terminal knob domain (AdGFPDeltaknob); and (iii) capsid components isolated from Ad5-infected cells or expressed as recombinant proteins, hexon, penton, penton base, full-length fiber, fiber knob, and fiber mutants. We found that penton capsomer (penton base linked to its fiber projection), full-length fiber protein, and its isolated knob domain were all capable of inducing DC maturation, whereas no significant DC maturation was observed for hexon or penton base alone. This capacity was severely reduced for AdGFPDeltaknob and for fiber protein deletion mutants lacking the beta-stranded region F of the knob (residues Leu-485-Thr-486). The DC maturation effect was fully retained in a recombinant fiber protein deleted of the HI loop (FiDeltaHI), a fiber (Fi) deletion mutant that failed to trimerize, suggesting that the fiber knob-mediated DC activation did not depend on the integrity of the HI loop and on the trimeric status of the fiber. Interestingly, peptide-pulsed DC that had been stimulated with Ad5 knob protein induced a potent CD8+ T cell response in vivo.
Molinier-Frenkel
Valérie
V
Département d'Immunologie, Institut Cochin, INSERM U567, CNRS UMR 8104, Laboratoire membre de l'Institut Fédératif de Recherche 116, Université R. Descartes, 27 rue du Faubourg Saint Jacques, 75014 Paris, France. valerie.frenkel@hmn.ap-hop-paris.fr
Prévost-Blondel
Armelle
A
Hong
Saw-See
SS
Lengagne
Renée
R
Boudaly
Sarah
S
Magnusson
Maria K
MK
Boulanger
Pierre
P
Guillet
Jean-Gérard
JG
D000260:Adenoviruses, Human / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry* / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D007114:Immunization; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D051193:Toll-Like Receptors
D036022:Capsid Proteins; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; C018315:hexon capsid protein, Adenovirus