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• W2895034645 abstract "Abstract T cells are thought to discriminate stimulatory versus non-stimulatory ligands by converting small changes in ligand binding half-life to large changes in cell activation. Such a kinetic proofreading model has been difficult to test directly, as existing methods of altering ligand binding half-life also change other potentially important biophysical parameters, most notably the stability of the receptor-ligand interaction under load. Here we develop an optogenetic approach to specifically tune the binding half-life of a light-responsive ligand to a chimeric antigen receptor without changing other binding parameters. By simultaneously manipulating binding half-life while controlling for receptor occupancy, we find that signaling is strongly gated by ligand binding half-life. Our results provide direct evidence of kinetic proofreading in ligand discrimination by T cells. One Sentence Summary Direct control of ligand binding half-life with light shows that lifetime, not occupancy, dominates T cell activation." @default.
• W2895034645 created "2018-10-12" @default.
• W2895034645 creator A5027431979 @default.
• W2895034645 creator A5039788638 @default.
• W2895034645 date "2018-10-02" @default.
• W2895034645 modified "2023-09-23" @default.
• W2895034645 title "Light-based tuning of ligand half-life supports kinetic proofreading model of T cell activation" @default.
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• W2895034645 doi "https://doi.org/10.1101/432864" @default.
• W2895034645 hasPublicationYear "2018" @default.
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