TY - JOUR
T1 - In vivo receptor-mediated delivery of a recombinant invasive bacterial toxoid to CD11c+CD8α-CD11bhigh dendritic cells
AU - Guermonprez, Pierre
AU - Fayolle, Catherine
AU - Rojas, Marie Jésus
AU - Rescigno, Maria
AU - Ladant, Daniel
AU - Leclerc, Claude
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Adhesion molecule
KW - Antigen presentation
KW - CTL
KW - Dendritic cell
KW - Processing
KW - Vaccination
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U2 - 10.1002/1521-4141(200211)32:11<3071::AID-IMMU3071>3.0.CO;2-A
DO - 10.1002/1521-4141(200211)32:11<3071::AID-IMMU3071>3.0.CO;2-A
M3 - Article
C2 - 12385027
AN - SCOPUS:0036857619
VL - 32
SP - 3071
EP - 3081
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -