Immunity to T cell receptor peptides: theory and applications.

In this review, we describe an anti-idiotypic regulatory mechanism that is naturally induced by the autoimmune disease process, and that can be boosted by injection of TCR peptides that mimic epitopes generated naturally from germline sequences. The striking similarities in the induction and characteristics of rodent and human T cells specific for TCR peptides support the generality of the observation, and enhance the probability that this immunoregulatory mechanism will have application in human organ-specific autoimmune diseases that are characterized by oligoclonal expression of TCR V genes. The major challenges that remain to be resolved to make the TCR peptide therapy more widely applicable include (1) establishing disease-relevant V gene biases in individual patients, (2) identifying biologically active TCR peptide sequences, and (3) demonstrating that the induction of anti-TCR peptide immunity in humans can reduce the pernicious activity of autoreactive T cells putatively directed at organ-specific target antigens.