An antibody to the aggregated synthetic prion protein peptide (PrP106-126) selectively recognises disease-associated prion protein (PrP-Sc) from human brain specimens

M. Jones, D. Wight, V. McLoughlin, Katherine Norrby, J.W. Ironside, J.G. Connolly, C.F. Farquhar, I.R. MacGregor, M.W. Head

Research output: Contribution to journalArticlepeer-review

Abstract

Human prion diseases are characterized by the conversion of the normal host cellular prion protein (PrPC) into an abnormal misfolded form [disease-associated prion protein (PrPSc)]. Antibodies that are capable of distinguishing between PrPC and PrPSc may prove to be useful, not only for the diagnosis of these diseases, but also for a better understanding of the molecular mechanisms involved in disease pathogenesis. In an attempt to produce such antibodies, we immunized mice with an aggregated peptide spanning amino acid residues 106 to 126 of human PrP (PrP106-126). We were able to isolate and single cell clone a hybridoma cell line (P1:1) which secreted an IgM isotype antibody [monoclonal antibody (mAb P1:1)] that recognized the aggregated, but not the monomeric form of the immunogen. When used in immunoprecipitation assays, the antibody did not recognize normal PrPC from non-prion disease brain specimens, but did selectively immunoprecipitate full-length PrPSc from cases of variant and sporadic Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker disease. These results suggest that P1:1 recognizes an epitope formed during the structural rearrangement or aggregation of the PrP that is common to the major PrPSc types found in the most common forms of human prion disease
Original languageUndefined/Unknown
Pages (from-to)293-302
Number of pages10
JournalBrain Pathology
Volume19
Issue number2
DOIs
Publication statusPublished - 2009

Keywords

  • Creutzfeldt-Jakob disease immunoprecipitation monoclonal antibody prion protein PrP106-126 Animals Antibodies, Monoclonal/ immunology Blotting, Western Brain Chemistry Cell Line Creutzfeldt-Jakob Syndrome/metabolism/physiopathology Enzyme-Linked Immunosorbent Assay Gerstmann-Straussler-Scheinker Disease/metabolism Humans Immunohistochemistry Immunoprecipitation Mice Mice, Knockout PrPC Proteins/ analysis/ immunology PrPSc Proteins/ analysis/ immunology Prion Diseases/diagnosis/ metabolism

Cite this