The Magnitude of TCR Engagement is a Critical Predictor of T Cell Anergy or Activation

Saied Mirshahidi, Laura C. Korb Ferris, Scheherazade Sadegh-Nasseri

Research output: Contribution to journalArticlepeer-review

Abstract

Fast dissociation rate of peptide-MHC complexes from TCR has commonly been accepted to cause T cell anergy. In this study, we present evidence that peptides that form transient complexes with HLA-DR1 induce anergy in T cell clones in vitro and specific memory T cells in vivo. We demonstrate that similar to the low densities of long-lived agonist peptide-MHC, short-lived peptide-MHC ligands induce anergy by engagement of ∼1000 TCR and activation of a similar pattern of intracellular signaling events. These data strongly suggest that short-lived peptides induce anergy by presentation of low densities of peptide-MHC complexes. Moreover, they suggest that the traditional antagonist peptides might also trigger anergy by a similar molecular mechanism. The use of short-lived peptides to induce T cells anergy is a potential strategy for the prevention or treatment of autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)5346-5355
Number of pages10
JournalJournal of Immunology
Volume172
Issue number9
DOIs
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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