Bordetella pertussis adenylate cyclase delivers chemically coupled CD8+ T-cell epitopes to dendritic cells and elicits CTL in vivo.
The adenylate cyclase (CyaA) produced by Bordetella pertussis is able to deliver CD8+ and CD4+ T-cell epitopes genetically grafted within the catalytic domain of the molecule into antigen presenting cells in vivo. We develop now a new approach in which peptides containing CD8+ epitopes are chemically linked to CyaA. We show that CTL responses were induced in mice immunized with CyaA bearing these CD8+ epitopes. Moreover, we demonstrate that the OVA257-264 CD8+ epitope chemically grafted to CyaA is presented to CD8+ T cells by a mechanism requiring (1) proteasome processing, (2) TAP and (3) neosynthesis of MHC class I molecules. Thus, this novel strategy represents a very versatile system as a single CyaA carrier protein could be easily and rapidly coupled to any desired synthetic peptide.
Fayolle
Catherine
C
Unité de Biologie des Régulations Immunitaires, INSERM E 352, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Bauche
Cécile
C
Ladant
Daniel
D
Leclerc
Claude
C
D037361:Adenylate Cyclase Toxin / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D000950:Antigens, Ly / Q000378:metabolism; D001428:Bacterial Vaccines / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D001886:Bordetella pertussis / Q000201:enzymology / Q000276:immunology*; D020126:Brefeldin A / Q000494:pharmacology; D016827:CD8 Antigens / Q000276:immunology; D020134:Catalytic Domain; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D006056:Golgi Apparatus / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D037361:Adenylate Cyclase Toxin; D000950:Antigens, Ly; D001428:Bacterial Vaccines; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D020126:Brefeldin A