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.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Time Factors
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Models, Biological
- Mice
- Lymphocyte Activation
- Kinetics
- Immunology
- Animals
- 3204 Immunology
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Time Factors
- T-Lymphocytes
- Receptors, Antigen, T-Cell
- Models, Biological
- Mice
- Lymphocyte Activation
- Kinetics
- Immunology
- Animals
- 3204 Immunology