The POM monoclonals: A comprehensive set of antibodies to non-overlapping prion protein epitopes

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  • PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is the only defined constituent of the transmissible agent causing prion diseases. Expression of PrPC in the host organism is necessary for prion replication and for prion neurotoxicity. Understanding prion diseases necessitates detailed structural insights into PrPC and PrPSc. Towards this goal, we have developed a comprehensive collection of monoclonal antibodies denoted POM1 to POM19 and directed against many different epitopes of mouse PrPC. Three epitopes are located within the N-terminal octarepeat region, one is situated within the central unstructured region, and four epitopes are discontinuous within the globular C-proximal domain of PrPC. Some of these antibodies recognize epitopes that are resilient to protease digestion in PrPSc. Other antibodies immunoprecipitate PrPC, but not PrPSc. A third group was found to immunoprecipitate both PrP isoforms. Some of the latter antibodies could be blocked with epitope-mimicking peptides, and incubation with an excess of these peptides allowed for immunochromatography of PrPC and PrPSc. Amino-proximal antibodies were found to react with repetitive PrPC epitopes, thereby vastly increasing their avidity. We have also created functional single-chain miniantibodies from selected POMs, which retained the binding characteristics despite their low molecular mass. The POM collection, thus, represents a unique set of reagents allowing for studies with a variety of techniques, including western blotting, ELISA, immunoprecipitation, conformation-dependent immunoassays, and plasmon surface plasmon resonance-based assays.

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    Attribution 4.0 International
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    • Polymenidou, M., Moos, R., Scott, M., Sigurdson, C., Shi, Y. -Z., Yajima, W., Hafner-Bratkovič, I., Jerala, R., Hornemann, S., Wuthrich, K., Bellon, A., Vey, M., Garen, G., James, M. N. G., Kav, N., & Aguzzi, A. (2008). The POM monoclonals: A comprehensive set of antibodies to non-overlapping prion protein epitopes. PLoS ONE, 3(12), e3872 [17 pages].
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