1887

Abstract

Prion diseases involve conversion of host-encoded cellular prion protein (PrP) to a disease-related isoform (PrP). Using recombinant human -PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrP and recognized epitopes between residues 93–105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human -PrP were more efficient in immunoprecipitating PrP than PrP, and some of them could also distinguish between different PrP glycoforms. Using these monoclonal antibodies, the physical association of PrP glycoforms was studied in normal brain and in the brains of humans and mice with prion disease. It was shown that while PrP glycoforms can be selectively immunoprecipitated, the differentially glycosylated molecules of native PrP are closely associated and always immunoprecipitate together. Furthermore, the ratio of glycoforms comprising immunoprecipitated native PrP from diverse prion strains was similar to those observed on denaturing Western blots. These studies are consistent with the view that the proportion of each glycoform incorporated into PrP is probably controlled in a strain-specific manner and that each PrP particle contains a mixture of glycoforms.

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2005-09-01
2019-11-22
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