Multivalent adaptor networks generate nanoscale organisation within T cell signalling condensates
Shirin AnsariiD, Pooja LaxmaniD, James C. WalshiD, Zhengmin YangiD, Andrea C. NuneziD, Jesse GoyetteiD
Abstract
Ligand engagement of the T cell receptor (TCR) triggers phosphorylation-dependent assembly of signalling complexes at the plasma membrane, yet how these assemblies are organised to coordinate signal propagation remains unclear. Here, using quantitative super-resolution imaging in primary human T cells, we show that phosphorylated TCR (pTCR) and linker for activation of T cells (pLAT) reside within micrometre-scale signalling condensates that exhibit defined nanoscale organisation. Within these condensates, pTCR and pLAT are spatially interleaved with characteristic spacing of [~]70-100 nm and display short-range dispersion rather than aggregation. Spatial cross-correlation analysis reveals that pLAT is organised around pTCR sites, consistent with a model in which activated TCRs act as local sources of LAT phosphorylation that nucleate condensate assembly. This organisation suggests that multivalent interactions and steric constraints generate structured, yet dynamic, reaction environments that couple receptor activation to downstream signalling. Together, our findings establish that TCR signalling condensates are not amorphous assemblies but possess intrinsic nanoscale architecture and support a general framework in which membrane-proximal signalling is regulated by spatially organised, multivalent assemblies.
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