Altered T cell receptor ligands trigger a subset of early T cell signals

Joshua D. Rabinowitz, Craig Beeson, Christoph Wülfing, Keri Tate, Paul M. Allen, Mark M. Davis, Harden M. McConnell

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

TCR ligands are complexes of peptides and MHC proteins on the surfaces of APCs. Some of these ligands cause T cell proliferation (agonists), while others block it (antagonists). We compared the acid release, calcium flux, and proliferation response of helper T cells to a variety of ligands. We found that all agonist ligands but not most antagonist ligands trigger acid release, a general indicator of early cellular activation. Only a subset of ligands triggering acid release cause sustained calcium flux, and only a subset of these ligands cause T cell proliferation. Antagonist ligands and anti-CD4 antibodies both effectively block T cell proliferation. However, significantly greater antagonist ligand or antibody concentrations are required to block acid release and initial calcium influx. These data demonstrate a hierarchy of early T cell signaling steps and show that altered TCR ligands can initiate some steps while blocking the completion of others.

Original languageEnglish
Pages (from-to)125-135
Number of pages11
JournalImmunity
Volume5
Issue number2
DOIs
StatePublished - Aug 1996

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