Expression of CD226 is associated to but not required for NK cell education

Nat Commun. 2017 May 31:8:15627. doi: 10.1038/ncomms15627.


DNAX accessory molecule-1 (DNAM-1, also known as CD226) is an activating receptor expressed on subsets of natural killer (NK) and T cells, interacts with its ligands CD155 or CD112, and has co-varied expression with inhibitory receptors. Since inhibitory receptors control NK-cell activation and are necessary for MHC-I-dependent education, we investigated whether DNAM-1 expression is also involved in NK-cell education. Here we show an MHC-I-dependent correlation between DNAM-1 expression and NK-cell education, and an association between DNAM-1 and NKG2A that occurs even in MHC class I deficient mice. DNAM-1 is expressed early during NK-cell development, precedes the expression of MHC-I-specific inhibitory receptors, and is modulated in an education-dependent fashion. Cd226-/- mice have missing self-responses and NK cells with a normal receptor repertoire. We propose a model in which NK-cell education prevents or delays downregulation of DNAM-1. This molecule endows educated NK cells with enhanced effector functions but is dispensable for education.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis*
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Cells, Cultured
  • Female
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • Nectins / metabolism
  • Neoplasms / immunology
  • Receptors, Virus / metabolism
  • beta 2-Microglobulin / genetics


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily C
  • Nectins
  • Receptors, Virus
  • beta 2-Microglobulin
  • poliovirus receptor