Progressive enhancement of kinetic proofreading in T cell antigen discrimination from receptor activation to DAG generation.

ABSTRACT: T cells use kinetic proofreading to discriminate antigens by converting small changes in antigen-binding lifetime into large differences in cell activation, but where in the signaling cascade this computation is performed is unknown. Previously, we developed a light-gated immune receptor to probe the role of ligand kinetics in T cell antigen signaling. We found significant kinetic proofreading at the level of the signaling lipid diacylglycerol (DAG) but lacked the ability to determine where the multiple signaling steps required for kinetic discrimination originate in the upstream signaling cascade (Tiseher and Weiner, 2019). Here, we uncover where kinetic proofreading is executed by adapting our optogenetic system for robust activation of early signaling events. We find the strength of kin

SUBMITTER: Britain DM 

PROVIDER: S-EPMC9536835 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature