Partial T cell signaling: altered phospho-zeta and lack of zap70 recruitment in APL-induced T cell anergy

Cell. 1994 Dec 2;79(5):913-22. doi: 10.1016/0092-8674(94)90080-9.


Studies of T cell responses to altered peptide ligands (APLs) have provided functional evidence that a T cell receptor (TCR) can interpret subtle changes in its ligand, resulting in different phenotypic outcomes. One dramatic effect of APL stimulation with live antigen-presenting cells (APCs) is the induction of energy as opposed to proliferation. We investigated the intracellular signaling events involved in generating this unresponsiveness by comparing protein-tyrosine phosphorylation patterns after stimulation with anergy-inducing APL or the immunogenic peptide. In resting T cell clones, presentation with APL/live APC stimulated a unique pattern of TCR phospho-zeta species and a subsequent lack of association with zap70. This demonstrates that the TCR-CD3 complex can engage selective intracellular biochemical signaling pathways as a direct consequence of the nature of the ligand recognized and the initial phosphotyrosine pattern of the TCR-CD3 proteins, leading to different phenotypes.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Clonal Anergy / immunology*
  • Hemoglobins / immunology
  • Ligands
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred Strains
  • Models, Immunological
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology*
  • ZAP-70 Protein-Tyrosine Kinase


  • Hemoglobins
  • Ligands
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • hemoglobin (64-76)
  • Protein-Tyrosine Kinases
  • ZAP-70 Protein-Tyrosine Kinase
  • Zap70 protein, mouse