TY - JOUR
T1 - Expression of CD226 is associated to but not required for NK cell education
AU - Wagner, Arnika K.
AU - Kadri, Nadir
AU - Snäll, Johanna
AU - Brodin, Petter
AU - Gilfillan, Susan
AU - Colonna, Marco
AU - Bernhardt, Günter
AU - Höglund, Petter
AU - Kärre, Klas
AU - Chambers, Benedict J.
PY - 2017/5/31
Y1 - 2017/5/31
N2 - 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 â '/â ' 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.
AB - 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 â '/â ' 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.
UR - http://www.scopus.com/inward/record.url?scp=85019994079&partnerID=8YFLogxK
U2 - 10.1038/ncomms15627
DO - 10.1038/ncomms15627
M3 - Article
C2 - 28561023
AN - SCOPUS:85019994079
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
M1 - 15627
ER -