Login / Signup

Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.

Darren B McAffeeMark K O'DairJenny J LinShalini T Low-NamKiera B WilhelmSungi KimShumpei MoritaJay T Groves
Published in: Nature communications (2022)
LAT assembly into a two-dimensional protein condensate is a prominent feature of antigen discrimination by T cells. Here, we use single-molecule imaging techniques to resolve the spatial position and temporal duration of each pMHC:TCR molecular binding event while simultaneously monitoring LAT condensation at the membrane. An individual binding event is sufficient to trigger a LAT condensate, which is self-limiting, and neither its size nor lifetime is correlated with the duration of the originating pMHC:TCR binding event. Only the probability of the LAT condensate forming is related to the pMHC:TCR binding dwell time. LAT condenses abruptly, but after an extended delay from the originating binding event. A LAT mutation that facilitates phosphorylation at the PLC-γ1 recruitment site shortens the delay time to LAT condensation and alters T cell antigen specificity. These results identify a function for the LAT protein condensation phase transition in setting antigen discrimination thresholds in T cells.
Keyphrases
  • single molecule
  • binding protein
  • regulatory t cells
  • dna binding
  • machine learning
  • healthcare
  • transcription factor
  • dendritic cells
  • protein protein
  • atomic force microscopy
  • photodynamic therapy
  • health information