The N-terminal sequence of prion protein consists an epitope specific to the abnormal isoform of prion protein (PrP(Sc))

The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by...

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Bibliographic Details
Published in:PloS one 2013-02, Vol.8 (2), p.e58013-e58013
Main Authors: Masujin, Kentaro, Kaku-Ushiki, Yuko, Miwa, Ritsuko, Okada, Hiroyuki, Shimizu, Yoshihisa, Kasai, Kazuo, Matsuura, Yuichi, Yokoyama, Takashi
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Animals
Antibodies, Monoclonal - immunology
Antibody Specificity
Biology
Bovine spongiform encephalopathy
Brain research
BSE
Cattle
Creutzfeldt-Jakob disease
Encephalopathy
Endopeptidase K
Epitope Mapping
Epitopes
Female
Immunization
Immunoglobulins
Medicine
Mice
Molecular Sequence Data
Monoclonal antibodies
Mutation
Ovis aries
Pathogenesis
Prion Diseases - metabolism
Prion protein
Protein structure
Proteinase
Proteins
PrPSc Proteins - chemistry
PrPSc Proteins - immunology
PrPSc Proteins - metabolism
Selectivity
Sheep
Veterinary Science
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Summary:The conformation of abnormal prion protein (PrP(Sc)) differs from that of cellular prion protein (PrP(C)), but the precise characteristics of PrP(Sc) remain to be elucidated. To clarify the properties of native PrP(Sc), we attempted to generate novel PrP(Sc)-specific monoclonal antibodies (mAbs) by immunizing PrP-deficient mice with intact PrP(Sc) purified from bovine spongiform encephalopathy (BSE)-affected mice. The generated mAbs 6A12 and 8D5 selectivity precipitated PrP(Sc) from the brains of prion-affected mice, sheep, and cattle, but did not precipitate PrP(C) from the brains of healthy animals. In histopathological analysis, mAbs 6A12 and 8D5 strongly reacted with prion-affected mouse brains but not with unaffected mouse brains without antigen retrieval. Epitope analysis revealed that mAbs 8D5 and 6A12 recognized the PrP subregions between amino acids 31-39 and 41-47, respectively. This indicates that a PrP(Sc)-specific epitope exists in the N-terminal region of PrP(Sc), and mAbs 6A12 and 8D5 are powerful tools with which to detect native and intact PrP(Sc). We found that the ratio of proteinase K (PK)-sensitive PrP(Sc) to PK-resistant PrP(Sc) was constant throughout the disease time course.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0058013