CIRCUMVENTING TOLERANCE TO GENERATE AUTOLOGOUS MONOCLONAL-ANTIBODIES TO THE PRION PROTEIN

Prion diseases are disorders of protein conformation and do not provok e an immune response. Raising antibodies to the prion protein (PrP) ha s been difficult due to conservation of the PrP sequence and to inhibi tory activity of alpha-PrP antibodies toward lymphocytes. To circumven t these problems, we immunized mice in which the PrP gene was ablated (Prnp(0/0)) and retrieved specific monoclonal antibodies (mAbs) throug h phage display libraries, This approach yielded alpha-PrP mAbs that r ecognize mouse PrP. Studies with these mAbs suggest that cellular PrP adopts an unusually open structure consistent with the conformational plasticity of this protein.