TY - JOUR
T1 - A dual function of NKG2D ligands in NK-cell activation
AU - Cheney, Elizabeth E.
AU - Wise, Erica L.
AU - Bui, Jack D.
AU - Schreiber, Robert D.
AU - Carayannopoulos, Leonidas N.
AU - Spitzer, Dirk
AU - Zafirova, Biljana
AU - Polic, Bojan
AU - Shaw, Andrey S.
AU - Markiewicz, Mary A.
PY - 2012/9
Y1 - 2012/9
N2 - NK-cell killing requires both the expression of activating receptor ligands and low MHC class I expression by target cells. Here we demonstrate that the expression of any of the murine ligands for the NK-cell activating receptor NKG2D results in a concomitant reduction in MHC class I expression. We show this both in tumor cell lines and in vivo. NK-cell lysis is enhanced by the decrease in MHC class I expression, suggesting the change is biologically relevant. These results demonstrate that NKG2D ligand expression on target cells not only allows for activating receptor recognition, but also actively reduces expression of the inhibitory ligand, MHC class I, leading to enhanced recognition and killing by NK cells.
AB - NK-cell killing requires both the expression of activating receptor ligands and low MHC class I expression by target cells. Here we demonstrate that the expression of any of the murine ligands for the NK-cell activating receptor NKG2D results in a concomitant reduction in MHC class I expression. We show this both in tumor cell lines and in vivo. NK-cell lysis is enhanced by the decrease in MHC class I expression, suggesting the change is biologically relevant. These results demonstrate that NKG2D ligand expression on target cells not only allows for activating receptor recognition, but also actively reduces expression of the inhibitory ligand, MHC class I, leading to enhanced recognition and killing by NK cells.
KW - MHC class I
KW - NK cells
KW - NKG2D ligands
UR - http://www.scopus.com/inward/record.url?scp=84865748478&partnerID=8YFLogxK
U2 - 10.1002/eji.201141849
DO - 10.1002/eji.201141849
M3 - Article
C2 - 22740149
AN - SCOPUS:84865748478
SN - 0014-2980
VL - 42
SP - 2452
EP - 2458
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 9
ER -