Non-infectious aggregates of the prion protein react with several PrP Sc-directed antibodies

Emiliano Biasini, M. Esa Seegulam, Brianna N. Patti, Laura Solforosi, Andrea Z. Medrano, Heather M. Christensen, Assunta Senatore, Roberto Chiesa, R. Anthony Williamson, David A. Harris

Research output: Contribution to journalArticlepeer-review

Abstract

The key event in the pathogenesis of prion diseases is the conformational conversion of the normal prion protein (PrP) (PrPC) into an infectious, aggregated isoform (PrPSc) that has a high content of β-sheet. Historically, a great deal of effort has been devoted to developing antibodies that specifically recognize PrPSc but not PrPC, as such antibodies would have enormous diagnostic and experimental value. A mouse monoclonal IgM antibody (designated 15B3) and three PrP motif-grafted monoclonal antibodies (referred to as IgG 19-33, 89-112, and 136-158) have been previously reported to react specifically with infectious PrPSc but not PrPC. In this study, we extend the characterization of these four antibodies by testing their ability to immunoprecipitate and immunostain infectious and non-infectious aggregates of wild-type, mutant, and recombinant PrP. We find that 15B3 as well as the motif-grafted antibodies recognize multiple types of aggregated PrP, both infectious and non-infectious, including forms found in brain, in transfected cells, and induced in vitro from purified recombinant protein. These antibodies are exquisitely selective for aggregated PrP, and do not react with soluble PrP even when present in vast excess. Our results suggest that 15B3 and the motif-grafted antibodies recognize structural features common to both infectious and non-infectious aggregates of PrP. Our study extends the utility of these antibodies for diagnostic and experimental purposes, and it provides new insight into the structural changes that accompany PrP oligomerization and prion propagation.

Original languageEnglish
Pages (from-to)2190-2204
Number of pages15
JournalJournal of Neurochemistry
Volume105
Issue number6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Monoclonal antibody
  • Prion
  • Prion protein
  • Protein aggregate
  • PrP

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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