Immune surveillance and antigen conformation determines humoral immune response to the prion protein immunogen

Transmissible spongiform encephalopathies (TSE) are progressive degenerativ e disorders of the central nervous system. PrPSc is a TSE-specific marker d erived from the host-encoded glycoprotein, PrPc. The generation of antibodi es to PrP plays an important role in the diagnosis of these diseases. In th is study the role of the PrP immunogen and the species being immunized was examined in relation to specific epitopes. Various mammals (mice, hamsters, rabbits and PrP null mice) were immunized with formic acid-treated PrPSc i solated from mice, hamsters and sheep. Both the species being immunized and the source of immunogen played an important role in the antibody response. Response to a limited number of linear epitopes was seen among the various immunized animals. One region in the C-terminal portion of PrP appeared hi ghly immunogenic in all species. Comparison of immunoreactivity and the pep scan-defined linear epitope sites suggests both linear and conformational d irected responses in many of the animals. Information on the forces directi ng immune responses to PrP will lead to a better understanding of host-PrP interactions. It will also assist in the development of new strategies for generating additional tools for immunodiagnosis.