Identification of two immunogenic domains of the prion protein--PrP--which activate class II-restricted T cells and elicit antibody responses against the native molecule.
Recent reports suggest that immunity against the prion protein (PrP) retards transmissible spongiform encephalopathies progression in infected mice. A major obstacle to the development of vaccines comes from the fact that PrP is poorly immunogenic, as it is seen as self by the host immune system. Additional questions concern the immune mechanisms involved in protection and the risk of eliciting adverse reactions in the central nervous system of treated patients. Peptide-based vaccines offer an attractive strategy to overcome these difficulties. We have undertaken the identification of the immunogenic regions of PrP, which trigger helper T cells (Th) associated with antibody production. Our results identify two main regions, one between the structured and flexible portion of PrP (98-127) and a second between alpha 1 and alpha 2 helix (143-187). Peptides (30-mer) corresponding to these regions elicit class II-restricted Th cells and antibody production against native PrP and could therefore be of potential interest for a peptide-based vaccination.
Gregoire
Sylvie
S
INSERM E209, Hôpital Saint-Antoine, Bâtiment Kourilsky, 184 rue du faubourg Saint-Antoine, 75571 Paris Cedex 12, France. carnaud@st-antoine.inserm.fr
Logre
Caroline
C
Metharom
Pat
P
Loing
Estelle
E
Chomilier
Jacques
J
Rosset
Martine Bruley
MB
Aucouturier
Pierre
P
Carnaud
Claude
C
D000595:Amino Acid Sequence; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D018984:Epitopes, T-Lymphocyte; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II; D051379:Mice; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000276:immunology; D018621:PrPC Proteins / Q000737:chemistry* / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014162:Transfection
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D019151:Peptide Library; D010455:Peptides; D018621:PrPC Proteins; D011994:Recombinant Proteins