Modulation of proteinase-K resistant prion protein by prion peptide immunization.
Prion diseases are caused by conformational alterations in the prion protein (PrP). The immune system has been assumed to be non-responsive to the self-prion protein, therefore, PrP autoimmunity has not been investigated. Here, we immunized various strains of mice with PrP peptides, some selected to fit the MHC class II-peptide binding motif. We found that specific PrP peptides elicited strong immune responses in NOD, C57BL/6 and A/J mice. To test the functional effect of this immunization, we examined the expression of proteinase-K-resistant PrP by a scrapie-infected tumor transplanted to immunized syngeneic A/J mice. PrP peptide vaccination did not affect the growth of the infected tumor transplant, but significantly reduced the level of protease-resistant PrP. Our results demonstrate that self-PrP peptides are immunogenic in mice and suggest that this immune response might affect PrP-scrapie levels in certain conditions.
Souan
L
L
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Tal
Y
Y
Felling
Y
Y
Cohen
I R
IR
Taraboulos
A
A
Mor
F
F
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D015551:Autoimmunity / Q000276:immunology; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D019286:Endopeptidase K / Q000378:metabolism*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D012608:Scrapie / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D010455:Peptides; D018620:PrPSc Proteins; D019286:Endopeptidase K