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

Michael Jones, Darren Wight, Victoria McLoughlin, Katherine Norrby, James W. Ironside, John G. Connolly, Christine F. Farquhar, Ian R. MacGregor, Mark W. Head

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.
LanguageEnglish
Pages293-302
Number of pages10
JournalBrain Pathology
Volume19
Issue number2
DOIs
Publication statusPublished - Apr 2009

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Prion Diseases
Peptides
Antibodies
Brain
Gerstmann-Straussler-Scheinker Disease
Creutzfeldt-Jakob Syndrome
Hybridomas
Brain Diseases
Immunoprecipitation
Immunoglobulin M
Epitopes
Clone Cells
Monoclonal Antibodies
Amino Acids
Cell Line
Prion Proteins

Keywords

  • creutzfeldt-jakob disease
  • immunoprecipitation
  • monoclonal antibody
  • prion protein
  • PrP106–126

Cite this

Jones, Michael ; Wight, Darren ; McLoughlin, Victoria ; Norrby, Katherine ; Ironside, James W. ; Connolly, John G. ; Farquhar, Christine F. ; MacGregor, Ian R. ; Head, Mark W. / An antibody to the aggregated synthetic prion protein peptide (PrP106-126) selectively recognizes disease-associated prion protein (PrPSc) from human brain specimens. In: Brain Pathology. 2009 ; Vol. 19, No. 2. pp. 293-302.
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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.",
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An antibody to the aggregated synthetic prion protein peptide (PrP106-126) selectively recognizes disease-associated prion protein (PrPSc) from human brain specimens. / Jones, Michael; Wight, Darren; McLoughlin, Victoria; Norrby, Katherine; Ironside, James W.; Connolly, John G.; Farquhar, Christine F.; MacGregor, Ian R.; Head, Mark W.

In: Brain Pathology, Vol. 19, No. 2, 04.2009, p. 293-302.

Research output: Contribution to journalArticle

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