Activation thresholds determine susceptibility to peptide-induced tolerance in a heterogeneous myelin-reactive T cell repertoire

David McCue, Kelli R Ryan, David C Wraith, Stephen M Anderton

Research output: Contribution to journalArticlepeer-review

Abstract

Altered peptide ligands (APL) with increased MHC-binding properties are highly effective at inducing T cell tolerance after systemic administration in soluble form, preventing experimental autoimmune encephalomyelitis (EAE) induced with the myelin basic protein (MBP) Ac1-9 peptide. We have previously described a diverse Ac1-9-reactive T cell repertoire with differing TCR affinities. A remaining question is what proportion of this repertoire is silenced by peptide therapy? Here, we show that the sensitivity of a T cell to peptide-induced tolerance is related to its avidity for native Ac1-9. These data provide new evidence that self-reactive T cells bearing low-affinity TCRs are able to escape therapeutic induction of tolerance.

Original languageEnglish
Pages (from-to)96-106
Number of pages11
JournalJournal of Neuroimmunology
Volume156
Issue number1-2
DOIs
Publication statusPublished - Nov 2004

Keywords

  • Animals
  • Autoantigens/administration & dosage
  • Cell Line
  • Dose-Response Relationship, Immunologic
  • Encephalomyelitis, Autoimmune, Experimental/immunology
  • Immune Tolerance
  • Immunity, Innate
  • Immunization
  • Lymphocyte Activation/immunology
  • Mice
  • Mice, Transgenic
  • Myelin Basic Protein/administration & dosage
  • Peptide Fragments/administration & dosage
  • T-Lymphocytes/immunology

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