Issue 9, 2022

The T cell receptor displays lateral signal propagation involving non-engaged receptors

Abstract

T cells are highly sensitive to low levels of antigen, but how this sensitivity is achieved is currently unknown. Here, we imaged proximal TCR-CD3 signal propagation with single molecule localization microscopy (SMLM) in T cells activated with nanoscale clusters of TCR stimuli. We observed the formation of large TCR-CD3 clusters that exceeded the area of the ligand clusters, and required multivalent interactions facilitated by TCR-CD3 phosphorylation for assembly. Within these clustered TCR-CD3 domains, TCR-CD3 signaling spread laterally for ∼500 nm, far beyond the activating site, via non-engaged receptors. Local receptor density determined the functional cooperativity between engaged and non-engaged receptors, but lateral signal propagation was not influenced by the genetic deletion of ZAP70. Taken together, our data demonstrates that clustered ligands induced the clustering of non-ligated TCR-CD3 into domains that cooperatively facilitate lateral signal propagation.

Graphical abstract: The T cell receptor displays lateral signal propagation involving non-engaged receptors

Supplementary files

Article information

Article type
Paper
Submitted
06 Sep 2021
Accepted
09 Feb 2022
First published
16 Feb 2022

Nanoscale, 2022,14, 3513-3526

The T cell receptor displays lateral signal propagation involving non-engaged receptors

D. J. Nieves, E. Pandzic, S. D. Gunasinghe, J. Goyette, D. M. Owen, J. Justin Gooding and K. Gaus, Nanoscale, 2022, 14, 3513 DOI: 10.1039/D1NR05855J

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