Altered T cell receptor ligands trigger a subset of early T cell signals.
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.
Rabinowitz
J D
JD
Department of Chemistry, Howard Hughes Medical Institute, Stanford University, California 94305, USA.
Beeson
C
C
Wülfing
C
C
Tate
K
K
Allen
P M
PM
Davis
M M
MM
McConnell
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003574:Cytochrome c Group / Q000276:immunology / Q000378:metabolism; D006454:Hemoglobins / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D003574:Cytochrome c Group; D006454:Hemoglobins; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D002118:Calcium