The role of antibodies to PrP in the diagnosis of transmissible spongiform encephalopathies.

Transmissible spongiform encephalopathies (TSE) are progressive degenerative disorders of the central nervous system. Efficient and accurate identification of these disorders is necessitated by their transmissibility and fatal prognosis. The availability of polyclonal and monoclonal antibodies to a TSE disease-specific protein marker PrPSC affords the sensitivity and specificity for immuno-diagnostic assays. The majority of PrPSC antigenic sites are species-directed, involve non-self sites and are common to both the normal host precursor (PrPC) and the modified disease form. The availability of these antigenic sites is highly restricted by conformational influences resulting in epitope-dependent restrictions on antibody binding. Diagnostic immunoassays for TSE have relied largely on immunocytochemistry and immunoblotting. Restrictions on epitope availability have lead to the formulation by several laboratories of a variety of techniques to unmask PrP specific epitopes. In addition, diagnosis requires the ability to detect PrPSC specifically in tissue which can also contain immuno-reactive PrPC. Immuno-detection techniques are discussed relative to their range of application, ease of interpretation, specificity and sensitivity.