A T–cell receptor (TCR) peptide vaccine from the Vβ5.2 sequence expressed in multiple sclerosis (MS) plaques and on myelin basic protein (MBP)–specific T cells boosted peptide–reactive T cells in patients with progressive MS. Vaccine responders had a reduced MBP response and remained clinically stable without side effects during one year of therapy, whereas nonresponders had an increased MBP response and progressed clinically. Peptide–specific T helper 2 cells directly inhibited MBP–specific T helper 1 cells in vitro through the release of interleukin–10, implicating a bystander suppression mechanism that holds promise for treatment of MS and other autoimmune diseases.