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

• Main Authors: McAffee, Darren B., O'Dair, Mark K., Lin, Jenny J., Low-Nam, Shalini T., Wilhelm, Kiera B., Kim, Sungi, Morita, Shumpei, Groves, Jay T.
• Other Authors: Institute for Digital Molecular Analytics and Science (IDMxS)
• Format: Article
• Language: English
• Published: 2023
• Subjects: Science::Biological sciences; Diffusion Magnetic Resonance Imaging; LAT Protein
• Online Access: https://hdl.handle.net/10356/170829
• Institution: Nanyang Technological University

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.