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 OVA(257-264) 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. (C) 2004 Elsevier Ltd. All rights reserved.