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

Author

Listed:
  • 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
    Nanyang Technological University)

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.

Suggested Citation

  • Darren B. McAffee & Mark K. O’Dair & Jenny J. Lin & Shalini T. Low-Nam & Kiera B. Wilhelm & Sungi Kim & Shumpei Morita & Jay T. Groves, 2022. "Discrete LAT condensates encode antigen information from single pMHC:TCR binding events," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35093-9
    DOI: 10.1038/s41467-022-35093-9
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    References listed on IDEAS

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    1. Yuanqing Ma & Elvis Pandzic & Philip R. Nicovich & Yui Yamamoto & Joanna Kwiatek & Sophie V. Pageon & Aleš Benda & Jérémie Rossy & Katharina Gaus, 2017. "An intermolecular FRET sensor detects the dynamics of T cell receptor clustering," Nature Communications, Nature, vol. 8(1), pages 1-11, April.
    2. Johannes B. Huppa & Markus Axmann & Manuel A. Mörtelmaier & Björn F. Lillemeier & Evan W. Newell & Mario Brameshuber & Lawrence O. Klein & Gerhard J. Schütz & Mark M. Davis, 2010. "TCR–peptide–MHC interactions in situ show accelerated kinetics and increased affinity," Nature, Nature, vol. 463(7283), pages 963-967, February.
    3. Jason Yi & Lakshmi Balagopalan & Tiffany Nguyen & Katherine M. McIntire & Lawrence E. Samelson, 2019. "TCR microclusters form spatially segregated domains and sequentially assemble in calcium-dependent kinetic steps," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    4. Shunsuke F. Shimobayashi & Pierre Ronceray & David W. Sanders & Mikko P. Haataja & Clifford P. Brangwynne, 2021. "Nucleation landscape of biomolecular condensates," Nature, Nature, vol. 599(7885), pages 503-506, November.
    5. Darrell J. Irvine & Marco A. Purbhoo & Michelle Krogsgaard & Mark M. Davis, 2002. "Direct observation of ligand recognition by T cells," Nature, Nature, vol. 419(6909), pages 845-849, October.
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