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 (K(D)) for the TCR, but vastly different potencies for T cell activation. Ligands with similar K(D)s 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.
Kersh, G. J., Kersh, E. N., Fremont, D. H., & Allen, P. M. (1998). High- and low-potency ligands with similar affinities for the TCR: The importance of kinetic in TCR signaling. Immunity, 9(6), 817–826. https://doi.org/10.1016/S1074-7613(00)80647-0