Detection of prion epitopes on PrPc and PrPsc of transmissible spongiform encephalopathies using specific monoclonal antibodies to PrP

Abstract

Amino acid residues 90-120 of the prion protein (PrP) are likely to be critical for the conversion of PrPc to PrPsc in the transmissible spongiform encephalopathies. We raised 10 monoclonal antibodies against the 90-120 amino acid region, mapped the epitope specificity of these anti-PrP antibodies, and investigated the expression of epitopes recognized by the antibodies in both PrPc and PrPsc. Four out of five of the anti-PrP antibodies raised in a prion knockout mouse immunized with the linear peptide of PrP90-120 could detect PrPsc in 'native' and denatured forms and PrPc in normal cells, as well as recognize epitopes within PrP93-112 residues. In contrast, the other six anti-PrP reagents,..