T-CELL RECEPTOR PEPTIDE THERAPY TRIGGERS AUTOREGULATION OF EXPERIMENTAL ENCEPHALOMYELITIS

Encephalitogenic T cells specific for myelin basic protein share common V-beta-8 peptide sequences in their T cell receptor (TCR) that can induce autoregulatory T cells and antibodies that prevent clinical signs of experimental autoimmune encephalomyelitis (EAE). It is not known, however, if TCR peptides can treat established disease. To test its therapeutic value, TCR-V-beta-8-39-59 peptide was injected into rats with clinical signs of EAE. This treatment reduced disease severity and speeded recovery, apparently by boosting anti-V-beta-8 T cells and antibodies raised naturally in response to encephalitogenic V-beta-8+ T cells. These results demonstrate that synthetic TCR be used therapeutically, and implicate the TCR-V-beta-8-39-59 sequence as a natural idiotope involved in EAE recovery. Similarly, human TCR peptides may be effective in enhancing natural regulation of autoreactive T cells that share common V genes.