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

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 and Jonathan Sprent ()
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Jae-Ho Cho: Academy of Immunology and Microbiology, Institute for Basic Science
Hee-Ok Kim: Academy of Immunology and Microbiology, Institute for Basic Science
Young-Jun Ju: Academy of Immunology and Microbiology, Institute for Basic Science
Yoon-Chul Kye: Academy of Immunology and Microbiology, Institute for Basic Science
Gil-Woo Lee: Academy of Immunology and Microbiology, Institute for Basic Science
Sung-Woo Lee: Academy of Immunology and Microbiology, Institute for Basic Science
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
Cecile King: Immunology Research Program, Garvan Institute of Medical Research
Jonathan Sprent: Pohang University of Science and Technology

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13373

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