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T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling

Author

Listed:
  • Shu Shien Chin

    (Albert Einstein College of Medicine, Department of Microbiology and Immunology)

  • Erik Guillen

    (Albert Einstein College of Medicine, Department of Microbiology and Immunology)

  • Laurent Chorro

    (Albert Einstein College of Medicine, Department of Microbiology and Immunology)

  • Sooraj Achar

    (Center for Cancer Research, ImmunoDynamics Group)

  • Karina Ng

    (Albert Einstein College of Medicine, Department of Microbiology and Immunology)

  • Susanne Oberle

    (Technical University of Munich)

  • Francesca Alfei

    (Technical University of Munich
    Lausanne University Hospital)

  • Dietmar Zehn

    (Technical University of Munich
    Lausanne University Hospital)

  • Grégoire Altan-Bonnet

    (Center for Cancer Research, ImmunoDynamics Group)

  • Fabien Delahaye

    (Albert Einstein College of Medicine, Department of Genetics
    Institut Pasteur de Lille, UMR1283/8199)

  • Grégoire Lauvau

    (Albert Einstein College of Medicine, Department of Microbiology and Immunology)

Abstract

Cognate antigen signal controls CD8+ T cell priming, expansion size and effector versus memory cell fates, but it is not known if and how it modulates the functional features of memory CD8+ T cells. Here we show that the strength of T cell receptor (TCR) signaling controls the requirement for interleukin-2 (IL-2) signals to form a pool of memory CD8+ T cells that competitively re-expand upon secondary antigen encounter. Combining strong TCR and intact IL-2 signaling during priming synergistically induces genome-wide chromatin accessibility in regions targeting a wide breadth of biological processes, consistent with greater T cell functional fitness. Chromatin accessibility in promoters of genes encoding for stem cell, cell cycle and calcium-related proteins correlates with faster intracellular calcium accumulation, initiation of cell cycle and more robust expansion. High-dimensional flow-cytometry analysis of these T cells also highlights higher diversity of T cell subsets and phenotypes with T cells primed with stronger TCR and IL-2 stimulation than those primed with weaker strengths of TCR and/or IL-2 signals. These results formally show that epitope selection in vaccine design impacts memory CD8+ T cell epigenetic programming and function.

Suggested Citation

  • Shu Shien Chin & Erik Guillen & Laurent Chorro & Sooraj Achar & Karina Ng & Susanne Oberle & Francesca Alfei & Dietmar Zehn & Grégoire Altan-Bonnet & Fabien Delahaye & Grégoire Lauvau, 2022. "T cell receptor and IL-2 signaling strength control memory CD8+ T cell functional fitness via chromatin remodeling," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29718-2
    DOI: 10.1038/s41467-022-29718-2
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    References listed on IDEAS

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