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Nat Commun. 2016 Nov 14;7:13373. doi: 10.1038/ncomms13373.

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

Author information

1
Academy of Immunology and Microbiology, Institute for Basic Science, Pohang 790-784, Korea.
2
Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang 790-784, Korea.
3
Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
4
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Korea.
5
La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.

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.

PMID:
27841348
PMCID:
PMC5114568
DOI:
10.1038/ncomms13373
[Indexed for MEDLINE]
Free PMC Article

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