The impact of duration versus extent of TCR occupancy on T cell activation: A revision of the kinetic proofreading model
The impact of duration versus extent of TCR occupancy on T cell activation: A revision of the kinetic proofreading model
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DOI：
10.1016/s1074-7613(01)00173-x
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发表时间：
2001-07-01
期刊：
影响因子：
32.4
通讯作者：
Jameson, SC
中科院分区：
文献类型：
--
作者：
Rosette, C;Werlen, G;Jameson, SC
广泛接受的动力学校正理论提出，从肽/MHC配体快速解离TOR允许刺激早期而不是晚期T细胞活化事件，这解释了为什么低亲和力TCR配体是差的激动剂。我们确定了一种低亲和力的TCR配体，它刺激晚期T细胞反应，但与动力学校正的预测相反，它不能有效地诱导早期激活事件。此外，由该配体诱导的反应与其高亲和力对应物相比在动力学上延迟。使用肽/MHC四聚体，我们表明，激活特性可以解离TOR占用肽/MHC配体。我们的数据表明，T细胞反应是由累积信号触发的，该信号在不同的时间点达到不同的TCR配体。
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.