Targeting the TCR: T-cell receptor and peptide-specific tolerance-based strategies for restoring self-tolerance in CNS autoimmune disease

Adam P. Kohm, Danielle M. Turley, Stephen D Miller*

*Corresponding author for this work

Research output: Contribution to journalReview article

13 Scopus citations


A principal theme in autoimmunity is the breakdown of central tolerance resulting in the persistence and eventual activation of autoreactive T cells. Because CD4+ T cells are key contributors to the underlying pathogenic mechanisms responsible for the onset and progression of most autoimmune diseases, they are a logical target for therapeutic interventions. One technique for restoring self-tolerance is to exploit the endogenous regulatory mechanisms that govern CD4+ T-cell activation. In this review, we discuss promising techniques with the common goal of inducing antigen (Ag)-specific tolerance. Emphasis is given to the use of non-mitogenic anti-CD3 and peptide-specific tolerance strategies that specifically target the T-cell receptor (TCR) in the absence of costimulatory signals. These approaches produce a TCR signal of insufficient strength to cause CD4+ T-cell activation and instead induce functional T-cell anergy or deletion while avoiding generalized long-term immunosuppression.

Original languageEnglish (US)
Pages (from-to)361-392
Number of pages32
JournalInternational Reviews of Immunology
Issue number5-6
Publication statusPublished - Sep 1 2005



  • Autoimmunity
  • Costimulation
  • Non-mitogenic anti-CD3
  • Regulatory T cells
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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