Partially phosphorylated T cell receptor ζ molecules can inhibit T cell activation

Ellen N. Kersh, Gilbert J. Kersh, Paul M. Allen

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

The T cell receptor complex (TCR) ζ chain is constitutively tyrosine phosphorylated specifically at two of the six ζ immunoreceptor tyrosine- based activation motif (ITAM) tyrosine residues in resting peripheral T cells. Further phosphorylation of ζ is induced by both agonist and antagonist ligands of the TCR, with agonists inducing complete phosphorylation of the ζ ITAM tyrosines. After antagonist stimulation, ζ phosphorylation is incomplete and generates discrete forms of partially phosphorylated ITAMs. Here, we mutate specific tyrosines in chimeric human CD8-ζ molecules to reflect phosphorylation in resting T cells as well as phosphorylation induced by agonist and antagonist ligands. We demonstrate that such partially phosphorylated TCR-ζ species can inhibit IL-2 production in T cell hybridomas and proliferation in T cell clones. This reveals a previously unrecognized, inhibitory function of partially phosphorylated ITAMs. These findings support the concept that TCR antagonism can arise through the generation of an inhibitory signal within the TCR complex and that constitutive ζ phosphorylation in resting T cells is an inhibitory signaling environment.

Original languageEnglish
Pages (from-to)1627-1636
Number of pages10
JournalJournal of Experimental Medicine
Volume190
Issue number11
DOIs
StatePublished - Dec 6 1999

Keywords

  • Altered peptide ligand
  • CD3 complex phosphorylation
  • ITAM
  • T cell signaling
  • TCR antagonism

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