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Clustering of the ?-Chain Can Initiate T Cell Receptor Signaling.

ABSTRACT: T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of ?-chain in a light controlled manner. We showed that spatial clustering of the ?-chain intracellular tail alone was sufficient to initialize T cell triggering including phosphorylation of ?-chain, Zap70, PLC?, ERK and initiated Ca2+ flux. In reconstituted COS-7 cells, only Lck expression was required to initiate ?-chain phosphorylation upon ?-chain clustering, which leads to the recruitment of tandem SH2 domain of Zap70 from cell cytosol to the newly formed ?-chain clusters at the plasma membrane. Taken together, our data demonstrated the biophysical relevance of receptor clustering in TCR signaling.

SUBMITTER: Ma Y

PROVIDER: S-EPMC7279048 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Clustering of the ζ-Chain Can Initiate T Cell Receptor Signaling.

Ma Yuanqing Y Lim Yean J YJ Benda Aleš A Lou Jieqiong J Goyette Jesse J Gaus Katharina K

International journal of molecular sciences 20200515 10

T cell activation is initiated when ligand binding to the T cell receptor (TCR) triggers intracellular phosphorylation of the TCR-CD3 complex. However, it remains unknown how biophysical properties of TCR engagement result in biochemical phosphorylation events. Here, we constructed an optogenetic tool that induces spatial clustering of ζ-chain in a light controlled manner. We showed that spatial clustering of the ζ-chain intracellular tail alone was sufficient to initialize T cell triggering inc ...[more]

PMID: 32429097

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