New insight into abnormal prion protein using monoclonal antibodies

Studies of abnormal prion protein (PrPres) are hindered by the lack of specific monoclonal antibodies (mAbs), and the relationships between PrPres, infectivity, and strain specificity in prion diseases are still subject to debate. We have studied PrPres with new mAbs produced against PrP in mice using various immunization strategies. PrPres was analyzed by Western blot with different prion strains in various hosts. Differences in the electrophoretic pattern of human PrPres revealed by these antibodies provide new insight into PrPres cleavage by proteases and interpretation of strain typing. This study confirms that the N-terminal extremity of PrPres is differentially sensitive to proteases, Conversely, the C-terminal extremity, which resists proteolysis, seems to be abnormally detectable by antibodies in ultrastructural studies. This work confirms the highly complex role of PrPres in prion diseases and provides new tools which will be made available to facilitate progress in qualitative and quantitative studies of PrP. (C) 1999 Academic Press.