Discrete LAT condensates encode antigen information from single pMHC:TCR binding events
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 conde...
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sg-ntu-dr.10356-1708292023-10-11T15:31:54Z Discrete LAT condensates encode antigen information from single pMHC:TCR binding events McAffee, Darren B. O'Dair, Mark K. Lin, Jenny J. Low-Nam, Shalini T. Wilhelm, Kiera B. Kim, Sungi Morita, Shumpei Groves, Jay T. Institute for Digital Molecular Analytics and Science (IDMxS) Science::Biological sciences Diffusion Magnetic Resonance Imaging LAT Protein 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. Published version Supported by NIH grant P01 AI091580 and by the Novo Nordisk Foundation under the Center for Geometrically Engineered Cellular Systems (NNF17OC0028176).The financial support for this work was provided by National Institutes of Health grant P01 AI091580 and by the Novo Nordisk Foundation Challenge Programme as part of the Center for Geometrically Engineered Cellular Systems. 2023-10-08T06:53:15Z 2023-10-08T06:53:15Z 2022 Journal Article McAffee, D. B., O'Dair, M. K., Lin, J. J., Low-Nam, S. T., Wilhelm, K. B., Kim, S., Morita, S. & Groves, J. T. (2022). Discrete LAT condensates encode antigen information from single pMHC:TCR binding events. Nature Communications, 13(1), 7446-. https://dx.doi.org/10.1038/s41467-022-35093-9 2041-1723 https://hdl.handle.net/10356/170829 10.1038/s41467-022-35093-9 36460640 2-s2.0-85143170336 1 13 7446 en Nature communications © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |
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Science::Biological sciences Diffusion Magnetic Resonance Imaging LAT Protein McAffee, Darren B. O'Dair, Mark K. Lin, Jenny J. Low-Nam, Shalini T. Wilhelm, Kiera B. Kim, Sungi Morita, Shumpei Groves, Jay T. Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
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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. |
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Institute for Digital Molecular Analytics and Science (IDMxS) |
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Institute for Digital Molecular Analytics and Science (IDMxS) McAffee, Darren B. O'Dair, Mark K. Lin, Jenny J. Low-Nam, Shalini T. Wilhelm, Kiera B. Kim, Sungi Morita, Shumpei Groves, Jay T. |
format |
Article |
author |
McAffee, Darren B. O'Dair, Mark K. Lin, Jenny J. Low-Nam, Shalini T. Wilhelm, Kiera B. Kim, Sungi Morita, Shumpei Groves, Jay T. |
author_sort |
McAffee, Darren B. |
title |
Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
title_short |
Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
title_full |
Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
title_fullStr |
Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
title_full_unstemmed |
Discrete LAT condensates encode antigen information from single pMHC:TCR binding events |
title_sort |
discrete lat condensates encode antigen information from single pmhc:tcr binding events |
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2023 |
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https://hdl.handle.net/10356/170829 |
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1781793668459397120 |