title: Breaking immune tolerance to the prion protein using prion protein peptides plus oligodeoxynucleotide-CpG in mice.
abstract: The absence of a detectable immune response during transmissible spongiform encephalopathies is likely due to the fact that the essential component of infectious agents, the prion protein (PrP), is a self Ag expressed on the surface of many cells of the host. To overcome self-tolerance to PrP, we used 30-mer PrP peptides previously shown to be immunogenic in Prnp(-/-) mice, together with CFA or CpG-oligodeoxynucleotides (CpG) in IFA. Generation of anti-PrP T and B cell responses was analyzed in the spleen, lymph nodes, and serum of immunized C57BL/6 wild-type mice. Immunization with PrP peptides emulsified in CFA did not trigger an immune response to PrP. When CpG were used, vaccination with peptides P143-172 and P158-187 generated IFN-gamma-secreting splenic T cells, and only P158-187 significantly stimulated IL-4-secreting T cells. Both peptides induced few Ab-producing B cells, and low and variable serum Ab titers. In contrast, immunization with peptide P98-127 did not induce significant levels of T cell responses but elicited specific peptide Abs. T cell epitope mapping, performed using 15-mer peptides covering PrP segment 142-182, revealed that an immunogenic motif lies between positions 156 and 172. These results demonstrate that T and B cell repertoires against PrP can be stimulated in C57BL/6 when adjuvant of the innate immunity such as CpG, but not CFA, is added to PrP peptides, and that the pattern of immune responses varies according to the epitope.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale and Université Pierre et Marie Curie, Hopital Saint-Antoine, Paris, France. rosset@st-antoine.inserm.fr
authors.forename: Martine Bruley
authors.initials: MB
authors.lastname: Rosset
authors.forename: Clara
authors.initials: C
authors.lastname: Ballerini
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gregoire
authors.forename: Pat
authors.initials: P
authors.lastname: Metharom
authors.forename: Claude
authors.initials: C
authors.lastname: Carnaud
authors.forename: Pierre
authors.initials: P
authors.lastname: Aucouturier
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology*; D011328:Prions / Q000008:administration & dosage* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D011328:Prions; D015847:Interleukin-4; D007371:Interferon-gamma