TY - JOUR
T1 - DAP10 associates with Ly49 receptors but contributes minimally to their expression and function in vivo
AU - Tassi, Ilaria
AU - Le Friec, Gaelle
AU - Gilfillan, Susan
AU - Takai, Toshiyuki
AU - Yokohama, Wayne M.
AU - Colonna, Marco
PY - 2009
Y1 - 2009
N2 - NK cells recognize target cells through activating receptors, many of which rely on the transmembrane adaptors DAP10, DAP12 and FcR-γ to deliver intracellular signals. Because these adaptors initiate distinct signaling pathways, they dictate the type of response mediated by receptor engagement. DAP10, for example, primarily triggers cytotoxicity, whereas DAP12 induces both cytotoxicity and IFN-γ secretion. In mice, NKG2D signals through both DAP10 and DAP12, which broadens and modulates the type of response engendered by encounter with ligand. Although initial studies indicated that Ly49H and Ly49D recruit only DAP12, a recent report suggested that they also associate with DAP10. We asked whether this association occurs and is functionally significant under physiologic conditions. Our data demonstrate that DAP10 does associate with Ly49H and Ly49D in primary NK cells. While this association contributes slightly to cell surface expression of both receptors, it has no significant impact on Ly49H-mediated control of murine cytomegalovirus infection. Thus, while many activating NK-cell receptors are promiscuous in terms of adaptor association, our data indicate that the functional consequences of such promiscuity may vary widely and may not be evident in all cases.
AB - NK cells recognize target cells through activating receptors, many of which rely on the transmembrane adaptors DAP10, DAP12 and FcR-γ to deliver intracellular signals. Because these adaptors initiate distinct signaling pathways, they dictate the type of response mediated by receptor engagement. DAP10, for example, primarily triggers cytotoxicity, whereas DAP12 induces both cytotoxicity and IFN-γ secretion. In mice, NKG2D signals through both DAP10 and DAP12, which broadens and modulates the type of response engendered by encounter with ligand. Although initial studies indicated that Ly49H and Ly49D recruit only DAP12, a recent report suggested that they also associate with DAP10. We asked whether this association occurs and is functionally significant under physiologic conditions. Our data demonstrate that DAP10 does associate with Ly49H and Ly49D in primary NK cells. While this association contributes slightly to cell surface expression of both receptors, it has no significant impact on Ly49H-mediated control of murine cytomegalovirus infection. Thus, while many activating NK-cell receptors are promiscuous in terms of adaptor association, our data indicate that the functional consequences of such promiscuity may vary widely and may not be evident in all cases.
KW - Cytomegalovirus
KW - Innate immunity
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=65449185938&partnerID=8YFLogxK
U2 - 10.1002/eji.200838972
DO - 10.1002/eji.200838972
M3 - Article
C2 - 19247984
AN - SCOPUS:65449185938
SN - 0014-2980
VL - 39
SP - 1129
EP - 1135
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 4
ER -