Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenylate Cyclase Toxin / immunology*
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Adenylate Cyclase Toxin / metabolism
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Animals
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Antigen Presentation / drug effects
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Antigens, Ly / metabolism
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Bacterial Vaccines / chemistry
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Bacterial Vaccines / immunology*
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Bacterial Vaccines / therapeutic use
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Bordetella pertussis / enzymology
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Bordetella pertussis / immunology*
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Brefeldin A / pharmacology
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CD8 Antigens / immunology
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Catalytic Domain
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology*
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Female
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Golgi Apparatus / metabolism
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Histocompatibility Antigens Class I / biosynthesis
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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T-Lymphocytes, Cytotoxic / immunology*
Substances
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Adenylate Cyclase Toxin
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Antigens, Ly
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Bacterial Vaccines
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CD8 Antigens
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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Ly6a protein, mouse
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Membrane Proteins
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Brefeldin A