Induction of T cell anergy by low numbers of agonist ligands

Laura C. Korb, Saied Mirshahidi, Kasra Ramyar, Amir A. Sadighi Akha, Scheherazade Sadegh-Nasseri

Research output: Contribution to journalArticle

Abstract

Engagement of TCR by its ligand, the MHC/peptide complex, causes T cell activation. T cells respond positively to stimulation with agonists, and are inhibited by antagonist MHC/peptide ligands. Failure to induce proper conformational changes in the TCR or fast TCR/MHC dissociation are the leading models proposed to explain anergy induction by antagonist ligands. In this study, we demonstrate that presentation of between 1 and 10 complexes of agonist/MHC II by unfixed APC induces T cell anergy that persists up to 7 days and has characteristics similar to anergy induced by antagonist ligand or TCR occupancy without costimulation. Furthermore, anergy-inducing doses of hemagglutinin 306-318 peptide led to the engagement of less than 1000 TCR/CD3 complexes. Thus, engagement of a subthreshold number of TCR by either a low density of agonist/MHC or a 2-3 orders of magnitude higher density of antagonist/MHC causes anergy. Moreover, we show that anergy induced by low agonist concentrations is inhibited in the presence of IL-2 or cyclosporin A, suggesting involvement of the calcineurin signaling pathway.

Original languageEnglish (US)
Pages (from-to)6401-6409
Number of pages9
JournalJournal of Immunology
Volume162
Issue number11
StatePublished - Jun 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Korb, L. C., Mirshahidi, S., Ramyar, K., Sadighi Akha, A. A., & Sadegh-Nasseri, S. (1999). Induction of T cell anergy by low numbers of agonist ligands. Journal of Immunology, 162(11), 6401-6409.