IMMUNITY TO TCR PEPTIDES IN MULTIPLE-SCLEROSIS .1. SUCCESSFUL IMMUNIZATION OF PATIENTS WITH SYNTHETIC V-BETA-5.2 AND V-BETA-6.1 CDR2 PEPTIDES

Immunization with disease-associated TCR V region peptides is an effec tive treatment for experimental autoimmune encephalomyelitis. Myelin b asic protein-specific T cells, which induce experimental autoimmune en cephalomyelitis in many animal strains, may be important in the pathog enesis of multiple sclerosis. Myelin basic protein-specific T cell clo nes from some multiple sclerosis patients preferentially use TCR V gen es from the V beta 5.2 and V beta 6.1 families. To assess the safety a nd immunogenicity of TCR V beta 5.2 and V beta 6.1 peptides, we inject ed 11 multiple sclerosis patients with varying doses of two synthetic peptides, TCR V beta 5.2(39-59) and V beta 6.1(39-59), encompassing th e CDR2 region of these V gene families. Low doses (100 to 300 mu g) of peptide induced T cell immunity in 7 of 11 patients to one or both pe ptides. Delayed type hypersensitivity skin responses to the peptides w ere 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 immunosuppr ession. Synthetic TCR V region peptides can induce T cell immunity saf ely in humans and may prove useful in treating human autoimmune diseas es.