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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rosette, C; Werlen, G; Daniels, MA; Holman, PO; Alam, SM; Travers, PJ; Gascoigne, NR; Palmer, E; Jameson, SC

Published Date

  • July 2001

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 59 - 70

PubMed ID

  • 11485738

Pubmed Central ID

  • 11485738

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(01)00173-x


  • eng

Conference Location

  • United States