Prion (PrPSc)-specific epitope defined by a monoclonal antibody.
Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal antibody, 15B3, that can discriminate between the normal and disease-specific forms of PrP. Such an antibody has been long sought as it should be invaluable for characterizing the infectious particle as well as for diagnosis of TSEs such as bovine spongiform encephalopathy (BSE) or Creutzfeldt-Jakob disease (CJD) in humans. 15B3 specifically precipitates bovine, murine or human PrPSc, but not PrPC, suggesting that it recognizes an epitope common to prions from different species. Using immobilized synthetic peptides, we mapped three polypeptide segments in PrP as the 15B3 epitope. In the NMR structure of recombinant mouse PrP, segments 2 and 3 of the 15B3 epitope are near neighbours in space, and segment 1 is located in a different part of the molecule. We discuss models for the PrPSc-specific epitope that ensure close spatial proximity of all three 15B3 segments, either by intermolecular contacts in oligomeric forms of the prion protein or by intramolecular rearrangement.
Korth
C
C
Prionics AG, University of Zürich, Switzerland. ckorth@hifo.unizh.ch
Stierli
B
B
Streit
P
P
Moser
M
M
Schaller
O
O
Fischer
R
R
Schulz-Schaeffer
W
W
Kretzschmar
H
H
Raeber
A
A
Braun
U
U
Ehrensperger
F
F
Hornemann
S
S
Glockshuber
R
R
Riek
R
R
Billeter
M
M
Wüthrich
K
K
Oesch
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity; D002417:Cattle; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018620:PrPSc Proteins / Q000276:immunology*; D011233:Precipitin Tests; D011328:Prions / Q000276:immunology; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D018985:Epitopes, B-Lymphocyte; D018620:PrPSc Proteins; D011328:Prions