NR AOXA
AU Moroncini,G.; Kanu,N.; Solforosi,L.; Abalos,G.C.; Telling,G.; Brockes,J.P.; Williamson,R.A.
TI Motif-grafted antibodies containing the replicative interface of PrP are specific for PrPsc
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-28
PT Konferenz-Poster
AB Monoclonal antibodies binding epitopes comprising residues 96-104 and 133-158 of PrPc potently inhibit prion propagation, presumably by preventing heterodimeric association of PrPc and PrPsc, suggesting these regions of PrPc may be critical components of the PrPc-PrPsc replicative interface. We reasoned that transplanting PrP sequence corresponding to these regions into a suitable carrier molecule, such as an antibody, could impart specific recognition of disease-associated forms of PrP. To test this hypothesis, polypeptides containing PrP sequence between residues 89-112 or 136-158 were independently used to replace the extended heavy-chain-complementarity-determining region 3 (HCDR3) of an IgG antibody specific for the envelope glycoprotein of HIV-1. We demonstrate here that the resulting engineered PrP-IgGs bind specifically to PrPsc and its protease-resistant core, but not to PrPc, other cellular components, or to HIV-1 envelope. PrPsc reactivity was abolished when the PrP 136-158 graft was randomly reordered, or N-terminally truncated. Our findings indicate residues within the 89-112 and 136-158 segments of PrPc are a key component of one face of the PrPc-PrPsc complex. PrPsc-specific antibodies produced by this novel approach may find widespread application in the study of prion biology and replication and in the detection of infectious prions in human and animal materials.
AD G. Moroncini, Laura Solforosi, Gil C. Abalos, R. Anthony Williamson (anthony@scripps.edu), Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA; N. Kanu, J.P. Brockes, University College London, UK; G. Telling, University of Kentucky, USA
SP englisch
PO Deutschland