Modulation of proteinase-K resistant prion protein by prion peptide immunization

Prion diseases are caused by conformational alterations in the prion protei n (PrP). The immune system has been assumed to be non-responsive to the sel f-prion protein, therefore, PrP autoimmunity has not been investigated. Her e, we immunized various strains of mice with PrP peptides, some selected to fit the MHC class II-peptide binding motif. We found that specific PrP pep tides elicited strong immune responses in NOD, C57BL/6 and A/J mice. To tes t the functional effect of this immunization, we examined the expression of proteinase-K-resistant PrP by a scrapie-infected tumor transplanted to imm unized syngeneic A/J mice. PrP peptide vaccination did not affect the growt h of the infected tumor transplant, but significantly reduced the level of protease-resistant PrP. Our results demonstrate that self-PrP peptides are immunogenic in mice and suggest that this immune response might affect PrP- scrapie levels in certain conditions.