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© Sandrine Etienne-Manneville
Photo prise à l'avant (dans la protrusion) d'astrocytes primaires de rat en migration. Marquage par immunofluorescence montrant en rouge, p150 Glued, une protéine associée aux extrémités 'plus' des microtubules et en vert la tubuline des microtubules. La photographie montre l'accumulation de p150 Glued à l'avant des cellules en migration, où la protéine pourrait participer à l'ancrage des microtubules à la membrane plasmique. Pour essayer de corriger, les dérèglements observés lors de la migration des cellules d'astrocytes tumuraux ou gliomes on cherche à connaitre les mécanismes moléculaires fondamentaux qui controlent la polarisation et la migration cellulaires.
Publication : European journal of immunology

In vivo receptor-mediated delivery of a recombinant invasive bacterial toxoid to CD11c + CD8 alpha -CD11bhigh dendritic cells.

Team: Biochemistry of Macromolecular Interactions
Team: Dendritic cells and adaptive immunity
Member: Pierre Guermonprez
Member: Daniel Ladant
Member: Claude Leclerc
Scientific Fields
Diseases
Organisms
Applications
Technique

Published in European journal of immunology - 01 Nov 2002

Guermonprez P, Fayolle C, Rojas MJ, Rescigno M, Ladant D, Leclerc C

Link to Pubmed [PMID] – 12385027

Eur J Immunol 2002 Nov; 32(11): 3071-81

The precise contribution of mouse dendritic cells (DC) CD8 alpha +CD11blow and CD8 alpha -CD11bhigh subsets to CTL priming is not fully defined. Here we show that CyaA, the adenylate cyclase toxin of Bordetella pertussis, an invasive bacterial toxin that binds cells through CD11b/CD18 can be exploited for the targeted delivery of an exogenous peptide to the CD8 alpha -CD11bhigh subset in vivo. Antigen (Ag) genetically inserted in the N-terminal domain of mutant CyaA devoid of catalytic activity, are targeted to CD8 alpha -CD11bhigh DC by the CD11b/CD18-dependent binding of CyaA to the cell surface. Ag is then presented by MHC class I molecules of CD8 alpha -CD11bhigh DC after a TAP-dependent, cytosolic processing. As a result, CTL are primed after a single injection, bypassing requirement for adjuvant, CD4+ T cell help and CD40 signaling. Beside the interest of the CyaA vector for vaccine development, these results show that Ag presentation focused on CD8 alpha -CD11bhigh DC in vivo is sufficient for eliciting a vigorous CTL response and that CD11b/CD18 could be a suitable surface molecule for targeting Ag to DC.