In vivo receptor-mediated delivery of a recombinant invasive bacterial toxoid to CD11c+CD8α-CD11bhigh dendritic cells

Pierre Guermonprez, Catherine Fayolle, Marie Jésus Rojas, Maria Rescigno, Daniel Ladant, Claude Leclerc

Research output: Contribution to journalArticle

Abstract

The precise contribution of mouse dendritic cells (DC) CD8α+CD11blow and CD8α-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 CD8α-CD11bhigh subset in vivo. Antigen (Ag) genetically inserted in the N-terminal domain of mutant CyaA devoid of catalytic activity, are targeted to CD8α-CD11bhigh DC by the CID11b/CD18-dependent binding of CyaA to the cell surface. Ag is then presented by MHC class I molecules of CD8α-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 CD8α-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.

Original languageEnglish
Pages (from-to)3071-3081
Number of pages11
JournalEuropean Journal of Immunology
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2002

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Keywords

  • Adhesion molecule
  • Antigen presentation
  • CTL
  • Dendritic cell
  • Processing
  • Vaccination

ASJC Scopus subject areas

  • Immunology

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