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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD5 Antigens / immunology
  • CD5 Antigens / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Immunologic Memory / immunology*
  • Interleukin-2 / genetics
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Leukocyte Common Antigens / immunology*
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation / immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism

Substances

  • CD5 Antigens
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Leukocyte Common Antigens