The impact of duration versus extent of TCR occupancy on T cell activation: a revision of the kinetic proofreading model.
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.
Rosette
C
C
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Werlen
G
G
Daniels
M A
MA
Holman
P O
PO
Alam
S M
SM
Travers
P J
PJ
Gascoigne
N R
NR
Palmer
E
E
Jameson
S C
SC
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
D011948:Receptors, Antigen, T-Cell