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, ca lcium 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 ac tivation. Only a subset of ligands triggering acid release cause susta ined calcium flux, and only a subset of these ligands cause T cell pro liferation. Antagonist ligands and anti-CD4 antibodies both effectivel y block T cell proliferation. However, significantly greater antagonis t ligand or antibody concentrations are required to block acid release and initial calcium influx. These data demonstrate a hierarchy of ear ly T cell signaling steps and show that altered TCR ligands can initia te some steps while blocking the completion of others.