The Impact of Duration versus Extent of TCR Occupancy on T Cell Activation: A Revision of the Kinetic Proofreading Model

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• 作者：Caridad Rosette ; Guy Werlen ; Mark A. Daniels ; Philmore O. Holman ; S. Munir Alam ; Paul J. Travers ; Nicholas R. J. Gascoigne ; Ed Palmer and Stephen C. Jameson
• 刊名：Immunity
• 出版年：2001
• 出版时间：July 2001
• 年：2001
• 卷：15
• 期：1
• 页码：59-70
• 全文大小：416 K

文摘

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.