Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse

Ligation of T cell receptor (TCR) to peptide-MHC (pMHC) complexes initiates signaling leading to T cell activation and TCR ubiquitination. Ubiquitinated TCR is then either internalized by the T cell or released toward the antigen-presenting cell (APC) in extracellular vesicles. How these distinct fa...

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Prif Awduron: Kvalvaag, A, Valvo, S, Céspedes, PF, Saliba, DG, Kurz, E, Korobchevskaya, K, Dustin, ML
Fformat: Journal article
Iaith:English
Cyhoeddwyd: National Academy of Sciences 2023
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author Kvalvaag, A
Valvo, S
Céspedes, PF
Saliba, DG
Kurz, E
Korobchevskaya, K
Dustin, ML
author_facet Kvalvaag, A
Valvo, S
Céspedes, PF
Saliba, DG
Kurz, E
Korobchevskaya, K
Dustin, ML
author_sort Kvalvaag, A
collection OXFORD
description Ligation of T cell receptor (TCR) to peptide-MHC (pMHC) complexes initiates signaling leading to T cell activation and TCR ubiquitination. Ubiquitinated TCR is then either internalized by the T cell or released toward the antigen-presenting cell (APC) in extracellular vesicles. How these distinct fates are orchestrated is unknown. Here, we show that clathrin is first recruited to TCR microclusters by HRS and STAM2 to initiate release of TCR in extracellular vesicles through clathrin- and ESCRT-mediated ectocytosis directly from the plasma membrane. Subsequently, EPN1 recruits clathrin to remaining TCR microclusters to enable trans-endocytosis of pMHC-TCR conjugates from the APC. With these results, we demonstrate how clathrin governs bidirectional membrane exchange at the immunological synapse through two topologically opposite processes coordinated by the sequential recruitment of ecto- and endocytic adaptors. This provides a scaffold for direct two-way communication between T cells and APCs.
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institution University of Oxford
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spelling oxford-uuid:98bc84dd-a72f-4114-8b6b-2735a237ba252023-07-03T14:30:08ZClathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:98bc84dd-a72f-4114-8b6b-2735a237ba25EnglishSymplectic ElementsNational Academy of Sciences2023Kvalvaag, AValvo, SCéspedes, PFSaliba, DGKurz, EKorobchevskaya, KDustin, MLLigation of T cell receptor (TCR) to peptide-MHC (pMHC) complexes initiates signaling leading to T cell activation and TCR ubiquitination. Ubiquitinated TCR is then either internalized by the T cell or released toward the antigen-presenting cell (APC) in extracellular vesicles. How these distinct fates are orchestrated is unknown. Here, we show that clathrin is first recruited to TCR microclusters by HRS and STAM2 to initiate release of TCR in extracellular vesicles through clathrin- and ESCRT-mediated ectocytosis directly from the plasma membrane. Subsequently, EPN1 recruits clathrin to remaining TCR microclusters to enable trans-endocytosis of pMHC-TCR conjugates from the APC. With these results, we demonstrate how clathrin governs bidirectional membrane exchange at the immunological synapse through two topologically opposite processes coordinated by the sequential recruitment of ecto- and endocytic adaptors. This provides a scaffold for direct two-way communication between T cells and APCs.
spellingShingle Kvalvaag, A
Valvo, S
Céspedes, PF
Saliba, DG
Kurz, E
Korobchevskaya, K
Dustin, ML
Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title_full Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title_fullStr Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title_full_unstemmed Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title_short Clathrin mediates both internalization and vesicular release of triggered T cell receptor at the immunological synapse
title_sort clathrin mediates both internalization and vesicular release of triggered t cell receptor at the immunological synapse
work_keys_str_mv AT kvalvaaga clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse
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AT cespedespf clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse
AT salibadg clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse
AT kurze clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse
AT korobchevskayak clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse
AT dustinml clathrinmediatesbothinternalizationandvesicularreleaseoftriggeredtcellreceptorattheimmunologicalsynapse