Immunoregulation of autoimmune disease by vaccination with T cell receptor peptides.

Restricted TCR gene usage in animal models of autoimmune disease has led to strategies for control of these diseases by targeting the idiotypic determinants within the TCR sequence. Rats can be rendered resistant to EAE by immunization with synthetic peptides representing sequences contained within the V beta, J alpha and VDJ beta regions of the TCR that are conserved among encephalitogenic T cells. We propose that the mechanism of immunoregulation thus produced results from the stimulation of an anticlonotypic response directed at endogenously synthesized TCR peptides presented by Class I MHC on the surface of the autoreactive T cell, and that this mechanism may be part of the natural immunoregulation of T cell responses. The experimental data demonstrate the utility of this therapeutic approach and its potential for treatment of any pathogenic condition mediated by specific, oligoclonal T cell populations.