Scrapie and cellular prion proteins share polypeptide epitopes

Abstract

Purified preparations of scrapie prions contain one major protein, PrP 27-30, and aggregates of rod-shaped structures. On the basis of the NH2-terminal amino acid sequence of PrP 27-30, a synthetic peptide (PrP-P1) was constructed. Monospecific rabbit antisera to PrP-P1 were found by immunoblotting to react with PrP 27-30 and its precursor (PrP 33-35Sc), as well as with a related protease-sensitive cellular homologue (PrP 33-35C). An enzyme-linked immunosorbent assay showed that rabbit antiserum to PrP 27-30 was more reactive with PrP 27-30 than with PrP-P1; conversely, antiserum to PrP-P1 was more reactive with the peptide than with the prion proteins. In addition, antibodies to PrP-P1 decorate purified prion rods and stain amyloid plaques in scrapie-infected hamster brain. The peptide epitopes shared by PrP 27-30, PrP 33-35Sc, and PrP 33-35C clearly establish a relationship among these three proteins.