The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model

Immunity. 2001 Jul;15(1):59-70. doi: 10.1016/s1074-7613(01)00173-x.


The widely accepted kinetic proofreading theory proposes that rapid TCR dissociation from a peptide/MHC ligand allows for stimulation of early but not late T cell activation events, explaining why low-affinity TCR ligands are poor agonists. We identified a low-affinity TCR ligand which stimulated late T cell responses but, contrary to predictions from kinetic proofreading, inefficiently induced early activation events. Furthermore, responses induced by this ligand were kinetically delayed compared to its high-affinity counterpart. Using peptide/MHC tetramers, we showed that activation characteristics could be dissociated from TCR occupancy by the peptide/MHC ligands. Our data argue that T cell responses are triggered by a cumulative signal which is reached at different time points for different TCR ligands.

Publication types

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

MeSH terms

  • Animals
  • Kinetics
  • Lymphocyte Activation*
  • Mice
  • Models, Biological
  • Receptors, Antigen, T-Cell / physiology*
  • T-Lymphocytes / immunology*
  • Time Factors


  • Receptors, Antigen, T-Cell