How special is a pathogenic CNS autoantigen? Immunization to many CNS self-antigens does not induce autoimmune...

Recent work has shown neuro-protective effects of immunization with self-CNS antigens in animal models of Alzheimer's disease, prion diseases and CNS trauma. The major concern with such an approach is the inadvertent induction of autoimmune disease. The present work was initiated to study the incidence of autoimmune disease associated with the induction of T cell autoimmunity to a panel of 70 peptides derived from CNS proteins. Using a MHC class II motif developed in our laboratory to identify candidate peptides, we selected 70 peptides from 40 different CNS proteins. The proteins were selected randomly and represented various biological functions (surface receptors, structural proteins, synaptic proteins, neurodegeneration related proteins). Each peptide was emulsified in CFA and injected to autoimmune-prone Lewis rats. Immunogenicity was verified by peptide-specific LN cell proliferation. In addition, T cell lines were generated for many peptides and tested by adoptive transfer. Except for the previously reported pathogenicity of beta-synuclein, none of the 68 peptides from 39 proteins was found to induce CNS disease in recipient rats. These findings underscore the efficiency of immunological regulation in preventing CNS autoimmune disease, and confirm the uniqueness of the well-known pathogenic CNS auto-antigens.