High- and low-potency ligands with similar affinities for the TCR: the importance of kinetics in TCR signaling

Immunity. 1998 Dec;9(6):817-26. doi: 10.1016/s1074-7613(00)80647-0.


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-zeta but distinct patterns of zeta phosphorylation. Lower potency ligands induce only incomplete phosphorylation of TCR zeta 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 zeta.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Hemoglobins / agonists
  • Hemoglobins / antagonists & inhibitors
  • Hemoglobins / genetics
  • Hemoglobins / metabolism*
  • Histocompatibility Antigens Class II / metabolism*
  • Kinetics
  • Ligands
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Peptide Fragments / agonists
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Phosphorylation
  • Protein Binding
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • Solubility


  • Hemoglobins
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Ligands
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • antigen T cell receptor, zeta chain
  • hemoglobin (64-76)