T cell receptor peptides in treatment of autoimmune disease: Rationale and potential

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55 Scopus citations

Abstract

The natural tendency in T cell-mediated autoimmune conditions to develop focused antigen-specific responses that over-utilize certain T cell receptor (TCR) V region segments prompts the induction of anti-TCR-specific T cells and antibodies that can inhibit the pathogenic T cells and promote recovery from disease. This natural regulatory network can be manipulated by injecting synthetic peptide vaccines that correspond to segments of the over-expressed V genes. In experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis (MS), the pathogenic T cells are directed at myelin components, including basic protein (MBP). In some strains such as the Lewis rat and the PL/J mouse, the encephalitogenic BP-specific T cells overexpress a particular V region gene (Vβ8.2) in their TCR. In vivo administration of Vβ8.2 peptides in rats or mice can prevent and treat EAE by boosting regulatory anti-Vβ8.2-specific T cells that inhibit but do not delete the encephalitogenic specificities. This regulation is mediated by soluble factors, suggesting that the presence of regulatory TCR-specific T cells within the target organ (the central nervous system) may inhibit not only the stimulating Vβ8.2+ T cells, but also bystander T cells bearing different V genes. Parallel studies in MS patients have revealed striking V gene biases among BP-specific T cell clones from some patients that provided a rationale for TCR peptide therapy. Injection of Vβ5.2 and Vβ6.1 peptides boosted the frequency of TCR peptide-specific T cells and reduced responses to BP, in some cases with clinical benefit, indicating the presence of an anti-TCR regulatory network in humans that may also be manipulated with TCR peptide therapy.

Original languageEnglish (US)
Pages (from-to)391-402
Number of pages12
JournalJournal of Neuroscience Research
Volume43
Issue number4
DOIs
StatePublished - Jan 1 1996

Keywords

  • EAE
  • MS
  • TCR

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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