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bioRxiv · 10.1101/2021.12.16.472676

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

McAffee, D. B.·O'Dair, M. K.·Lin, J. J.·Low-Nam, S. T.·Wilhelm, K. B.·Kim, S.·Morita, S.·Groves, J. T.
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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-{gamma}1 recruitment site shortens the delay time to LAT condensation and alters T cell antigen specificity. These results identify a role for the LAT protein condensation phase transition in setting antigen discrimination thresholds in T cells.

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McAffee, D. B., O'Dair, M. K., Lin, J. J., Low-Nam, S. T., Wilhelm, K. B., Kim, S., Morita, S., Groves, J. T.. 2021-12-16. Discrete LAT condensates encode antigen information from single pMHC:TCR binding events. https://doi.org/10.1101/2021.12.16.472676

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