4.8 Article

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

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IMMUNITY
卷 15, 期 1, 页码 59-70

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CELL PRESS
DOI: 10.1016/S1074-7613(01)00173-X

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  1. NIAID NIH HHS [AI38903, T32 AI-07313] Funding Source: Medline
  2. NIGMS NIH HHS [GM394766] Funding Source: Medline

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The widely accepted kinetic proofreading theory proposes that rapid TOR 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 TOR 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.

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