Heterogeneity of Abnormal Prion Protein (PrP^Sc) in Murine Scrapie Prions Determined by PrP^Sc-Specific Monoclonal Antibodies

Abstract

In prion diseases, abnormal prion protein (PrP^Sc) is considered as the main component of the infectious agent. Delineation of PrP^Sc conformation is expected to be a critical factor in understanding properties of prions. However, practical methods to differentiate between conformers of PrP^Sc are inadequate. Here, we used two PrP^Sc-specific monoclonal antibodies (mAbs), 3B7 and 3H6, and found that mAb 3H6 detected a limited portion of PrP^Sc in five mice-adapted prion strains. The quantity of mAb 3H6-precipitated PrP^Sc was significantly lesser in 22L compared to other strains. This result provides a direct evidence of the conformational heterogeneity of PrP^Sc within the prion strains. Conformation-specific probes, like these mAbs, have the potential to be powerful tools for investigating conformational variations in PrP^Sc.