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

Arnika K. Wagner, Nadir Kadri, Johanna Snäll, Petter Brodin, Susan Gilfillan, Marco Colonna, Günter Bernhardt, Petter Höglund, Klas Kärre and Benedict J. Chambers ()
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Arnika K. Wagner: Tumor and Cell Biology, Karolinska Institutet
Nadir Kadri: Center for Hematology and Regenerative Medicine, Karolinska Institutet
Johanna Snäll: Center for Infectious Medicine, Karolinska Institutet, F59
Petter Brodin: Science for Life Laboratory, Karolinska Institutet, and Unit of Infectious Diseases, Karolinska University Hospital
Susan Gilfillan: Campus Box 8118, Washington University School of Medicine
Marco Colonna: Campus Box 8118, Washington University School of Medicine
Günter Bernhardt: Institute of Immunology, Building 11, Hannover Medical School
Petter Höglund: Center for Hematology and Regenerative Medicine, Karolinska Institutet
Klas Kärre: Tumor and Cell Biology, Karolinska Institutet
Benedict J. Chambers: Center for Infectious Medicine, Karolinska Institutet, F59

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/ncomms15627

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