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Conformational variation between allelic variants of cell-surface ovine prion protein
- Source :
- Biochemical Journal. 381:221-229
- Publication Year :
- 2004
- Publisher :
- Portland Press Ltd., 2004.
-
Abstract
- The distribution of prion infectivity and PrPSc between peripheral lymphoid tissues suggests their possible haematogenic spread during the progression of natural scrapie in susceptible sheep. Since ovine PBMCs (peripheral blood mononuclear cells) express PrPC, they have the potential to carry or harbour disease-associated forms of PrP. To detect the possible presence of disease-associated PrP on the surface of blood cells, an understanding is required of the conformations that normal ovine cell-surface PrPC may adopt. In the present study, we have used monoclonal antibodies that recognize epitopes in either the N- or C-terminal portions of PrP to probe the conformations of PrPC on ovine PBMCs by flow cytometry. Although PBMCs from scrapie-susceptible and -resistant genotypes of sheep expressed similar levels of cell-surface PrPC, as judged by their reactivity with N-terminal-specific anti-PrP monoclonal antibodies, there was considerable genotypic heterogeneity in the region between helix-1 and residue 171. Cells from PrP-VRQ (V136R154Q171) sheep showed uniform reactivity with monoclonal antibodies that bound to epitopes around helix-1, whereas cells from PrP-ARQ (A136R154Q171) and PrP-ARR (A136R154R171) sheep showed variable binding. The region between β-strand-2 and residue 171, which includes a YYR motif, was buried or obscured in cell-surface PrPC on PBMCs from scrapie-susceptible and -resistant sheep. However, an epitope of PrPC that is influenced by residue 171 was more exposed on PBMCs from PrP-VRQ sheep than on PBMCs from the PrP-ARQ genotype. Our results highlight conformational variation between scrapie-susceptible and -resistant forms of cell-surface PrPC and also between allelic variants of susceptible genotypes.
- Subjects :
- Genotype
Prions
Protein Conformation
medicine.drug_class
animal diseases
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Scrapie
Biology
Monoclonal antibody
Biochemistry
Peripheral blood mononuclear cell
Epitope
Flow cytometry
law.invention
Antigen-Antibody Reactions
Epitopes
Mice
law
medicine
Animals
Genetic Predisposition to Disease
PrPC Proteins
Molecular Biology
Alleles
Sheep, Domestic
medicine.diagnostic_test
Antibodies, Monoclonal
Genetic Variation
Membrane Proteins
Cell Biology
Virology
Molecular biology
Immunity, Innate
Recombinant Proteins
nervous system diseases
Blot
Leukocytes, Mononuclear
biology.protein
Recombinant DNA
Female
Antibody
Research Article
Subjects
Details
- ISSN :
- 14708728 and 02646021
- Volume :
- 381
- Database :
- OpenAIRE
- Journal :
- Biochemical Journal
- Accession number :
- edsair.doi.dedup.....1db1f89b50764afc5f287a3950e36c65
- Full Text :
- https://doi.org/10.1042/bj20040351