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Journal of Virology, November 1998, p. 9413-9418, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mapping the Prion Protein Using Recombinant Antibodies

R. Anthony Williamson,1 David Peretz,2 Clemencia Pinilla,3 Hadyn Ball,2 Raiza B. Bastidas,1 Roman Rozenshteyn,1 Richard A. Houghten,3 Stanley B. Prusiner,2,4 and Dennis R. Burton1,5,*

Departments of Immunology1 and Molecular Biology,5 The Scripps Research Institute, La Jolla, California 92037; Departments of Neurology2 and Biochemistry and Biophysics,4 University of California, San Francisco, California 94143; and Torrey Pines Institute for Molecular Studies, San Diego, California 921213

Received 11 May 1998/Accepted 30 July 1998

The fundamental event in prion disease is thought to be the posttranslational conversion of the cellular prion protein (PrPC) into a pathogenic isoform (PrPSc). The occurrence of PrPC on the cell surface and PrPSc 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 (Prnp0/0) 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 PrPC 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 PrPC and PrPSc, while epitopes associated with most of the antibodies in the panel were present on PrPC but absent from PrPSc.

* Corresponding author. Mailing address: Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (619) 784-9298. Fax: (619) 784-8360. E-mail: burton{at}scripps.edu.

Journal of Virology, November 1998, p. 9413-9418, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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