Immunity to TCR peptides in multiple sclerosis: I. Successful immunization of patients with synthetic Vβ5.2 and Vβ6.1 CDR2 peptides

Immunization with disease-associated TCR V region peptides is an effective treatment for experimental autoimmune encephalomyelitis. Myelin basic protein-specific T cells, which induce experimental autoimmune encephalomyelitis in many animal strains, may be important in the pathogenesis of multiple sclerosis. Myelin basic protein-specific T cell clones from some multiple sclerosis patients preferentially use TCR V genes from the Vβ5.2 and Vβ6.1 families. To assess the safety and immunogenicity of TCR Vβ5.2 and Vβ6.1 peptides, we injected 11 multiple sclerosis patients with varying doses of two synthetic peptides, TCR Vβ5.2_39-59 and Vβ6.1_39-59, encompassing the CDR2 region of these V gene families. Low doses (100 to 300 μg) of peptide induced T cell immunity in 7 of 11 patients to one or both peptides. Delayed type hypersensitivity skin responses to the peptides were observed in three of seven responders, and TCR peptide-specific Ab occurred in two of seven T cell responders. Low doses of TCR peptides produced no side effects and did not cause broad spectrum immunosuppression. Synthetic TCR V region peptides can induce T cell immunity safely in humans and may prove useful in treating human autoimmune diseases.