TY - JOUR
T1 - Altered T cell receptor ligands trigger a subset of early T cell signals
AU - Rabinowitz, Joshua D.
AU - Beeson, Craig
AU - Wülfing, Christoph
AU - Tate, Keri
AU - Allen, Paul M.
AU - Davis, Mark M.
AU - McConnell, Harden M.
N1 - Funding Information:
We thank J. Hampl for help starting this project, D. Lyons and J. Boniface for the altered MCC peptides and advice, and M. Liang for many valuable discussions. This work was supported by the Medical Scientist Training Program (J. D. R.), the Cancer Research Institute (C. B.), the European Molecular Biology Organization (C. W.), and grants from the National Institutes of Health. Peptides were characterized at the Mass Spectroscopy Facilities at the University of California, San Francisco.
PY - 1996/8
Y1 - 1996/8
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(00)80489-6
DO - 10.1016/S1074-7613(00)80489-6
M3 - Article
C2 - 8769476
AN - SCOPUS:0030218942
SN - 1074-7613
VL - 5
SP - 125
EP - 135
JO - Immunity
JF - Immunity
IS - 2
ER -