Novel epitopes identified by anti-PrP monoclonal antibodies produced following immunization of Prnp0/0 balb/cJ mice with purified scrapie prions
- Author(s): Stanker, LH
- Scotcher, MC
- Lin, A
- McGarvey, J
- Prusiner, SB
- Hnasko, R
- et al.
Published Web Locationhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3482378/
Prions, or infectious proteins, cause a class of uniformly fatal neurodegenerative diseases. Prions are composed solely of an aberrantly folded isoform (PrPSc) of a normal cellular protein (PrPC). Shared sequence identity of PrPSc with PrPC has limited the detection sensitivity of immunochemical assays, as antibodies specific for the disease-causing PrPSc isoform have not been developed. Here we report the generation of three new monoclonal antibodies (MAbs) to PrP, which were isolated following immunization of Prnp0/0 Balb/cJ mice with highly purified PrPSc isolated from brain lipid rafts. Epitope mapping using synthetic PrP peptides revealed that the three MAbs bind different epitopes of PrP. The DRM1-31 MAb has a conformational epitope at the proposed binding site for the putative prion conversion co-factor "protein X." The DRM1-60 MAb binds a single linear epitope localized to the β2-α2 loop region of PrP, whereas DRM2-118 binds an epitope that includes sequences within the octarepeat region and near the site of N-terminal truncation of PrPSc by proteinase K. Our novel anti-PrP MAbs with defined PrP epitopes may be useful in deciphering the conformational conversion of PrP C into PrPSc. © Copyright 2012, Mary Ann Liebert, Inc. 2012.
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