New insight into abnormal prion protein using monoclonal antibodies

Studies of abnormal prion protein (PrPres) are hindered by the lack of spec ific monoclonal antibodies (mAbs), and the relationships between PrPres, in fectivity, and strain specificity in prion diseases are still subject to de bate. We have studied PrPres with new mAbs produced against PrP in mice usi ng various immunization strategies. PrPres was analyzed by Western blot wit h different prion strains in various hosts. Differences in the electrophore tic pattern of human PrPres revealed by these antibodies provide new insigh t into PrPres cleavage by proteases and interpretation of strain typing. Th is study confirms that the N-terminal extremity of PrPres is differentially sensitive to proteases, Conversely, the C-terminal extremity, which resist s proteolysis, seems to be abnormally detectable by antibodies in ultrastru ctural studies. This work confirms the highly complex role of PrPres in pri on diseases and provides new tools which will be made available to facilita te progress in qualitative and quantitative studies of PrP. (C) 1999 Academ ic Press.