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Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation

Author

Listed:
  • Simon Zenke

    (Albert-Ludwigs-University
    Albert-Ludwigs-University
    Matterhorn Biosciences GmbH)

  • Mauricio P. Sica

    (Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

  • Florian Steinberg

    (Albert-Ludwigs-University Freiburg)

  • Julia Braun

    (Albert-Ludwigs-University
    Albert-Ludwigs-University)

  • Alicia Zink

    (Albert-Ludwigs-University)

  • Alina Gavrilov

    (Max Planck Institute of Immunobiology and Epigenetics
    Roche Innovation Center Basel)

  • Alexander Hilger

    (Albert-Ludwigs-University)

  • Aditya Arra

    (Otto-von-Guericke-University)

  • Monika Brunner-Weinzierl

    (Otto-von-Guericke-University)

  • Roland Elling

    (Albert-Ludwigs-University)

  • Niklas Beyersdorf

    (University of Würzburg)

  • Tim Lämmermann

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Cristian R. Smulski

    (Centro Atómico Bariloche, Comisión Nacional de Energía Atómica (CNEA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET))

  • Jan C. Rohr

    (Albert-Ludwigs-University
    Novartis Pharma AG)

Abstract

Intercellular communication is crucial for collective regulation of cellular behaviors. While clustering T cells have been shown to mutually control the production of key communication signals, it is unclear whether they also jointly regulate their availability and degradation. Here we use newly developed reporter systems, bioinformatic analyses, protein structure modeling and genetic perturbations to assess this. We find that T cells utilize trogocytosis by competing antagonistic receptors to differentially control the abundance of immunoregulatory ligands. Specifically, ligands trogocytosed via CD28 are shuttled to the T cell surface, enabling them to co-stimulate neighboring T cells. In contrast, CTLA4-mediated trogocytosis targets ligands for degradation. Mechanistically, this fate separation is controlled by different acid-sensitivities of receptor-ligand interactions and by the receptor intracellular domains. The ability of CD28 and CTLA4 to confer different fates to trogocytosed ligands reveals an additional layer of collective regulation of cellular behaviors and promotes the robustness of population dynamics.

Suggested Citation

  • Simon Zenke & Mauricio P. Sica & Florian Steinberg & Julia Braun & Alicia Zink & Alina Gavrilov & Alexander Hilger & Aditya Arra & Monika Brunner-Weinzierl & Roland Elling & Niklas Beyersdorf & Tim Lä, 2022. "Differential trafficking of ligands trogocytosed via CD28 versus CTLA4 promotes collective cellular control of co-stimulation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34156-1
    DOI: 10.1038/s41467-022-34156-1
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    References listed on IDEAS

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    1. Philippe E. Mangeot & Valérie Risson & Floriane Fusil & Aline Marnef & Emilie Laurent & Juliana Blin & Virginie Mournetas & Emmanuelle Massouridès & Thibault J. M. Sohier & Antoine Corbin & Fabien Aub, 2019. "Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9-sgRNA ribonucleoproteins," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
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