title: The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: C
authors.initials: C
authors.lastname: Rosette
authors.forename: G
authors.initials: G
authors.lastname: Werlen
authors.forename: M A
authors.initials: MA
authors.lastname: Daniels
authors.forename: P O
authors.initials: PO
authors.lastname: Holman
authors.forename: S M
authors.initials: SM
authors.lastname: Alam
authors.forename: P J
authors.initials: PJ
authors.lastname: Travers
authors.forename: N R
authors.initials: NR
authors.lastname: Gascoigne
authors.forename: E
authors.initials: E
authors.lastname: Palmer
authors.forename: S C
authors.initials: SC
authors.lastname: Jameson
mesh_terms: D000818:Animals; D007700:Kinetics; D008213:Lymphocyte Activation; D051379:Mice; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D011948:Receptors, Antigen, T-Cell