Multivalent adaptor networks generate nanoscale organisation within T cell signalling condensates

Area of Science:

• Immunology
• Cell Biology
• Molecular Signaling

Background:

• T cell receptor (TCR) engagement initiates signaling complex assembly at the plasma membrane.
• The precise organization of these signaling assemblies for effective signal propagation is not fully understood.

Purpose of the Study:

• To investigate the nanoscale organization of T cell receptor (TCR) signaling complexes within primary human T cells.
• To elucidate the spatial relationship between phosphorylated TCR (pTCR) and phosphorylated linker for activation of T cells (pLAT) during T cell activation.

Main Methods:

• Quantitative super-resolution imaging was employed in primary human T cells.
• Spatial cross-correlation analysis was used to determine the spatial organization of pTCR and pLAT within signaling condensates.

Main Results:

• Phosphorylated TCR (pTCR) and phosphorylated linker for activation of T cells (pLAT) form micrometre-scale signaling condensates.
• Within condensates, pTCR and pLAT exhibit defined nanoscale organization, spatially interleaved with ~70-100 nm spacing.
• pLAT is organized around pTCR sites, suggesting activated TCRs nucleate condensate assembly and LAT phosphorylation.

Conclusions:

• TCR signaling condensates possess intrinsic nanoscale architecture, not merely amorphous assemblies.
• This organization creates structured, dynamic reaction environments essential for coupling receptor activation to downstream signaling.
• Findings support a framework where membrane-proximal signaling is regulated by spatially organized, multivalent assemblies.