Immunomodulation of the human prion peptide 106-126 aggregation

Site-directed monoclonal antibodies (mAbs) may interact with their antigens , leading to stabilization, refolding, and suppression of aggregation. In t he following study, we show that mAbs raised against the peptide 106-126 of human prion protein (PrP 106-126) modulate the conformational changes occu rring in the peptide exposed to aggregation conditions. MAbs 3-11 and 2-40 prevent PrP 106-126's fibrillar aggregation, disaggregates already formed a ggregates, and inhibits the peptide's neurotoxic effect on the PC12 cells s ystem, while mAb 3F4 has no protective effect. We suggest that there are ke y positions within the PrP 106-126 molecule where unfolding is initiated an d their locking with specific antibodies may maintain the prion peptide nat ive structure, reverse the aggregated peptide conformation, and lead to rea rrangements involved in the essential feature of prion diseases. (C) 2001 A cademic Press.