Monoclonal Antibody against a Peptide of Human Prion Protein Discriminates between Creutzfeldt-Jacob's Disease-affected and Normal Brain Tissue
2004
Abstract Current methods for diagnosing transmissible spongiform encephalopathies rely on the degradation of the cellular prion protein (PrPC) and the subsequent detection of the protease-resistant remnant of the pathological prion isoform PrPSc by antibodies that react with all forms of PrP. We report on a monoclonal antibody, V5B2, raised against a peptide from the C-terminal part of PrP, which recognizes an epitope specific to PrPSc. In cryostat sections from Creutzfeldt-Jacob's disease (CJD) patients' brains, V5B2 selectively labels various deposits of PrPSc without any pretreatment for removal of PrPC. V5B2 does not bind to non-CJD brain samples or to recombinant PrP, either in its native or denatured form. Specificity for PrP is confirmed by a sandwich enzyme-linked immunosorbent assay utilizing V5B2, which discriminates between CJD and normal samples without proteinase K treatment, and by immunoprecipitation from CJD brain homogenate. The PrPSc-specific epitope is disrupted by denaturation. We conclude that the C-terminal part of PrP in disease-associated PrPSc aggregates forms a structural epitope whose conformation is distinct from that of PrPC.
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