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

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,