2024
DOI: 10.1101/2024.04.01.587588
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Differential Roles of Kinetic On- and Off-Rates in T-Cell Receptor Signal Integration Revealed with a Modified Fab’-DNA Ligand

Kiera B. Wilhelm,
Anand Vissa,
Jay T. Groves

Abstract: Antibody-derived T-cell receptor (TCR) agonists are commonly used to activate T cells. While antibodies can trigger TCRs regardless of clonotype, they bypass native T cell signal integration mechanisms that rely on monovalent, membrane-associated, and relatively weakly-binding ligand in the context of cellular adhesion. Commonly used antibodies and their derivatives bind much more strongly than native peptide-MHC (pMHC) ligands bind their cognate TCRs. Because ligand dwell time is a critical parameter that tig… Show more

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Cited by 2 publications
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“…After T cell adhesion and spreading into a nascent immunological synapse, pMHC:TCR binding events began to occur. pMHC has a slow binding on-rate to TCR (in contrast to anti-TCR Fab' or antibody (60,61)), and individual pMHC:TCR binding events were well spread out in time. LAT condensation and calcium signals initially remained low.…”
Section: Simultaneous Imaging Of Pmhc:tcr Lat Condensation and Calciu...mentioning
confidence: 99%
“…After T cell adhesion and spreading into a nascent immunological synapse, pMHC:TCR binding events began to occur. pMHC has a slow binding on-rate to TCR (in contrast to anti-TCR Fab' or antibody (60,61)), and individual pMHC:TCR binding events were well spread out in time. LAT condensation and calcium signals initially remained low.…”
Section: Simultaneous Imaging Of Pmhc:tcr Lat Condensation and Calciu...mentioning
confidence: 99%