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

Immunity. 1996 Aug;5(2):125-35. doi: 10.1016/s1074-7613(00)80489-6.


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.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD4 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Calcium / metabolism
  • Cell Line
  • Cytochrome c Group / immunology
  • Cytochrome c Group / metabolism
  • Hemoglobins / immunology
  • Hemoglobins / metabolism
  • Ligands
  • Lymphocyte Activation*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Moths / immunology
  • Receptors, Antigen, T-Cell / agonists
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction / immunology*


  • Antibodies, Monoclonal
  • CD4 Antigens
  • Cytochrome c Group
  • Hemoglobins
  • Ligands
  • Receptors, Antigen, T-Cell
  • Calcium