Differential CD3 zeta phosphorylation is not required for the induction of T cell antagonism by altered peptide ligands

J Immunol. 1999 Jul 15;163(2):599-602.


T cells recognize foreign Ags in the form of short peptides bound to MHC molecules. Ligation of the TCR:CD3 complex gives rise to the generation of two tyrosine-phosphorylated forms of the CD3 zeta-chain, pp21 and pp23. Replacement of residues in MHC-bound peptides that alter its recognition by the TCR can generate altered peptide ligands (APL) that antagonize T cell responses to the original agonist peptide, leading to altered T cell function and anergy. This biological process has been linked to differential CD3zeta phosphorylation and generation of only the pp21 phospho-species. Here, we show that T cells expressing CD3zeta mutants, which cannot be phosphorylated, exhibit a 5-fold reduction in IL-2 production and a 30-fold reduction in sensitivity following stimulation with an agonist peptide. However, these T cells are still strongly antagonized by APL. These data demonstrate that: 1) the threshold required for an APL to block a response is much lower than for an agonist peptide to induce a response, 2) CD3zeta is required for full agonist but not antagonist responses, and 3) differential CD3zeta phosphorylation is not a prerequisite for T cell antagonism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation
  • Clonal Anergy / immunology*
  • Cytoplasm / immunology
  • Cytoplasm / metabolism
  • Hybridomas
  • Interleukin-2 / biosynthesis
  • Ligands
  • Lymphocyte Activation / immunology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • Transfection / immunology
  • Tyrosine / metabolism


  • Interleukin-2
  • Ligands
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • Tyrosine