Immunohistochemical study of kuru plaques using antibodies against synthetic prion protein peptides

Summary Prion protein (PrP) is a protein closely associated with the transmission of scrapie and Creutzfeldt-Jakob disease (CJD). Kuru plaques are composed of this protein. PrP33–35 is converted to proteaseresistant PrP27–30 by proteinase K digestion. It has not yet been determined which of these PrPs is present in kuru plaques in vivo. Accordingly we synthesized two peptides (peptide-N and peptide-M) that, respectively, corresponded to the protease-sensitive and proteaseresistant portions of PrP33–35, based on the amino acid sequence deduced from human PrP cDNA. These two synthetic peptides were used to immunize rabbits and produce antisera (anti-N and anti-M). Both antisera stained kuru plaques in a patient with Gerstmann-Sträussler syndrome and one with CJD. Peptide-N has an amino acid sequence which does not exist in PrP27–30. Staining of kuru plaques by the antiserum against peptide-N indicated that the entire molecule, including the N-terminal portion of PrP33–35, was deposited in the kuru plaques.