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

Darren B. McAffee, Mark K. O’Dair, Jenny J. Lin, Shalini T. Low-Nam, Kiera B. Wilhelm, Sungi Kim, Shumpei Morita and Jay T. Groves ()
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Darren B. McAffee: University of California, Berkeley
Mark K. O’Dair: University of California, Berkeley
Jenny J. Lin: University of California, Berkeley
Shalini T. Low-Nam: University of California, Berkeley
Kiera B. Wilhelm: University of California, Berkeley
Sungi Kim: University of California, Berkeley
Shumpei Morita: University of California, Berkeley
Jay T. Groves: University of California, Berkeley

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-35093-9

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