Self prion protein peptides are immunogenic in Lewis rats

Prion diseases are caused by abnormal folding of the prion protein. The paradigm is that the prion protein is not immunogenic because the immune system must be tolerant to such a self protein. In an attempt to identify immunogenic prion peptides, we immunized Lewis rats with peptides that fitted the MHC class II RT1.B(1)motif. Both humoral and cellular immunity to the prion peptides were obtained without any harmful effects to young animals. However, when 8-month-old rats were immunized, a sixth (6/36) of the rats developed severe skin inflammation with concomitant hair loss. These findings suggest that immunity to self-prion peptides can be readily induced in Lewis rats and that this immune response may have pathogenic consequences in older rats.