High- and Low-Potency Ligands with Similar Affinities for the TCR: The Importance of Kinetics in TCR Signaling

Abstract

We have examined binding characteristics for a single TCR interacting with five of its different peptide/MHC ligands using surface plasmon resonance. We find that very small structural changes produce ligands with similar equilibrium binding affinities (KD) for the TCR, but vastly different potencies for T cell activation. Ligands with similar KDs induce similar amounts of total phospho-ζ but distinct patterns of ζ phosphorylation. Lower potency ligands induce only incomplete phosphorylation of TCR ζ and generally have faster off-rates. Therefore, the potency of TCR ligands is primarily determined by the half-life of the TCR-ligand complex and the consequent ability to induce complete phosphorylation of ζ.