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CD45-mediated control of TCR tuning in naïve and memory CD8+ T cells

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  • Jae-Ho Cho

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology
    Immunology Research Program, Garvan Institute of Medical Research)

  • Hee-Ok Kim

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Immunology Research Program, Garvan Institute of Medical Research)

  • Young-Jun Ju

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Seoul National University)

  • Yoon-Chul Kye

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Seoul National University)

  • Gil-Woo Lee

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology)

  • Sung-Woo Lee

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology)

  • Cheol-Heui Yun

    (Seoul National University)

  • Nunzio Bottini

    (La Jolla Institute for Allergy and Immunology)

  • Kylie Webster

    (Immunology Research Program, Garvan Institute of Medical Research)

  • Christopher C. Goodnow

    (Immunology Research Program, Garvan Institute of Medical Research)

  • Charles D. Surh

    (Academy of Immunology and Microbiology, Institute for Basic Science
    Pohang University of Science and Technology
    La Jolla Institute for Allergy and Immunology)

  • Cecile King

    (Immunology Research Program, Garvan Institute of Medical Research)

  • Jonathan Sprent

    (Pohang University of Science and Technology
    Immunology Research Program, Garvan Institute of Medical Research)

Abstract

Continuous contact with self-major histocompatibility complex (MHC) ligands is essential for survival of naïve T cells but not memory cells. This surprising finding implies that T cell subsets may vary in their relative T-cell receptor (TCR) sensitivity. Here we show that in CD8+T cells TCR sensitivity correlates inversely with levels of CD5, a marker for strong self-MHC reactivity. We also show that TCR sensitivity is lower in memory CD8+ T cells than naïve cells. In both situations, TCR hypo-responsiveness applies only to short-term TCR signalling events and not to proliferation, and correlates directly with increased expression of a phosphatase, CD45 and reciprocal decreased expression of activated LCK. Inhibition by high CD45 on CD8+ T cells may protect against overt TCR auto-MHC reactivity, while enhanced sensitivity to cytokines ensures strong responses to foreign antigens.

Suggested Citation

  • Jae-Ho Cho & Hee-Ok Kim & Young-Jun Ju & Yoon-Chul Kye & Gil-Woo Lee & Sung-Woo Lee & Cheol-Heui Yun & Nunzio Bottini & Kylie Webster & Christopher C. Goodnow & Charles D. Surh & Cecile King & Jonatha, 2016. "CD45-mediated control of TCR tuning in naïve and memory CD8+ T cells," Nature Communications, Nature, vol. 7(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13373
    DOI: 10.1038/ncomms13373
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    Cited by:

    1. Gil-Woo Lee & Young Ju Kim & Sung-Woo Lee & Hee-Ok Kim & Daeun Kim & Jiyoung Kim & You-Me Kim & Keunsoo Kang & Joon Haeng Rhee & Ik Joo Chung & Woo Kyun Bae & In-Jae Oh & Deok Hwan Yang & Jae-Ho Cho, 2024. "Developmental self-reactivity determines pathogenic Tc17 differentiation potential of naive CD8+ T cells in murine models of inflammation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Young-Jun Ju & Sung-Woo Lee & Yoon-Chul Kye & Gil-Woo Lee & Hee-Ok Kim & Cheol-Heui Yun & Jae-Ho Cho, 2021. "Self-reactivity controls functional diversity of naive CD8+ T cells by co-opting tonic type I interferon," Nature Communications, Nature, vol. 12(1), pages 1-15, December.

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