Mapping the prion protein using recombinant antibodies

R. Anthony Williamson, David Peretz, Clemencia Pinilla, Hadyn Ball, Raiza B. Bastidas, Roman Rozenshteyn, Richard A. Houghten, Stanley B. Prusiner, Dennis R. Burton

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Abstract

The fundamental event in prion disease is thought to be the posttranslational conversion of the cellular prion protein (PrP(C)) into a pathogenic isoform (PrP(Sc)). The occurrence of PrP(C) on the cell surface and PrP(Sc) in amyloid plaques in situ or in aggregates following purification complicates the study of the molecular events that underlie the disease process. Monoclonal antibodies are highly sensitive probes of protein conformation which can be used under these conditions. Here, we report the rescue of a diverse panel of 19 PrP-specific recombinant monoclonal antibodies from phage display libraries prepared from PrP deficient (Prnp(0/0)) mice immunized with infectious prions either in the form of rods or PrP 27-30 dispersed into liposomes. The antibodies recognize a number of distinct linear and discontinuous epitopes that are presented to a varying degree on different PrP preparations. The epitope reactivity of the recombinant PrP(90-231) molecule was almost indistinguishable from that of PrP(C) on the cell surface, validating the importance of detailed structural studies on the recombinant molecule. Only one epitope region at the C terminus of PrP was well presented on both PrP(C) and PrP(Sc), while epitopes associated with most of the antibodies in the panel were present on PrP(C) but absent from PrP(Sc).

Original languageEnglish (US)
Pages (from-to)9413-9418
Number of pages6
JournalJournal of virology
Volume72
Issue number11
StatePublished - Nov 1 1998

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Williamson, R. A., Peretz, D., Pinilla, C., Ball, H., Bastidas, R. B., Rozenshteyn, R., Houghten, R. A., Prusiner, S. B., & Burton, D. R. (1998). Mapping the prion protein using recombinant antibodies. Journal of virology, 72(11), 9413-9418.