NR AOQU
AU Bruley Rosset,M.; Ballerini,C.; Metharom,P.; Gregoire,S.; Carnaud,C.; Aucouturier,P.
TI Breaking tolerance to cellular PrP in C57BL/6 mice using PrP peptides associated with CpG
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-113
PT Konferenz-Poster
AB
The absence of an immune response during transmissible spongiform encephalopathies is likely due to the fact that the normal isoform of prion protein (PrPc) is a self-antigen expressed on the surface of a wide variety of cells. We recently demonstrated that immunisation of PrP knock out (Prpn -/-) mice with plasmid DNA encoding the mouse PrP could generate both T- and B-cell responses. The T-cell response was directed to 3 peptides out of a library of thirteen overlapping 30-mers encompassing the entire PrP sequence. However, this approach was not successful in eliciting an immune response in wild-type C57BL/6 (B6) mice.
In this study we showed that PrP peptide immunisation of B6 mice could lead to a specific immune response when CpG oligonucleotides, but not complete Freund's adjuvant, were employed as adjuvants. Vaccination with overlapping peptides 142-171 and 157-182 generated IFN-gamma and IL-4 secreting splenic T-cells and few antibody-producing B-cells. In contrast, peptide 92-126 did not increase significantly the number of IFN-gamma and IL-4 secreting T-cells but induced anti-PrP antibody production. T-cell epitope mapping, performed using a library of 15-mer peptides covering residues 142 to 182, revealed that the immunogenic sequence lay between position 157-171, a sequence shared by the two T-cell stimulating peptides. Antibody isotype typing revealed a predominance of IgG2b antibodies suggesting a Th2-type response to peptide 92-126. These results demonstrate that the tolerance to PrP can be overcome when peptide immunisation is associated with CpG, and that the type of response is dependent on the peptide. Currently, we are in the process of examining the efficiency T-cell response versus antibody response on the progress of the disease in mice infected with a murine scrapie strain.
AD M. Bruley Rosset, Clara Ballerini, INSERM E209, Paris France; Pat Metharom, Sir Albert Sakzewski Virus Research Centre, Royal Children's Hospital, Brisbane, Queensland 4029, Australia; Sylvie Gregoire, Institut National de la Sante et de la Recherche Medicale Unite 712 and Universite Pierre et Marie Curie, Hopital Saint-Antoine, Paris, France; Claude Carnaud (carnaud@necker.fr), Institut National de la Sante et de la Recherche Medicale Unite 25, Hopital Necker, Paris, France; Pierre Aucouturier (aucouturier@necker.fr), Institut National de la Sante et de la Recherche Medicale (INSERM) U25 and Centre National de la Recherche Scientifique U8603, Hopital Necker, Paris, France
SP englisch
PO Deutschland