TY - JOUR
T1 - Role of NKG2D in tumor cell lysis mediated by human NK cells
T2 - Cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin
AU - Pende, Daniela
AU - Cantoni, Claudia
AU - Rivera, Paola
AU - Vitale, Massimo
AU - Castriconi, Roberta
AU - Marcenaro, Stefania
AU - Nanni, Marina
AU - Biassoni, Roberto
AU - Bottino, Cristina
AU - Moretta, Alessandro
AU - Moretta, Lorenzo
PY - 2001
Y1 - 2001
N2 - NKG2D is a recently described activating receptor expressed by both NK cells and CTL. In this study we investigated the role of NKG2D in the natural cytolysis mediated by NK cell clones. The role of NKG2D varied depending on the type of target cells analyzed. Lysis of various tumors appeared to be exclusively natural cytotoxicity receptors (NCR) dependent. In contrast, killing of another group of target cells, including not only the epithelial cell lines HELA and IGROV-1, but also the FO-1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even normal PHA-induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell clones expressing low surface densities of NCR (NCRdull) could lyse these tumors in an exclusively NKG2D-dependent fashion. Remarkably, not all of these targets expressed MICA/B, thus implying the existence of additional ligands recognized by NKG2D, possibly represented by GPI-linked molecules. Finally, we show that the engagement of different HLA class I-specific inhibitory receptors by either specific antibodies or the appropriate HLA class I ligand led to inhibition of NKG2D-mediated NK cell triggering.
AB - NKG2D is a recently described activating receptor expressed by both NK cells and CTL. In this study we investigated the role of NKG2D in the natural cytolysis mediated by NK cell clones. The role of NKG2D varied depending on the type of target cells analyzed. Lysis of various tumors appeared to be exclusively natural cytotoxicity receptors (NCR) dependent. In contrast, killing of another group of target cells, including not only the epithelial cell lines HELA and IGROV-1, but also the FO-1 melanoma, the JA3 leukemia, the Daudi Burkitt lymphoma and even normal PHA-induced lymphoblasts, involved both NCR and NKG2D. Notably, NK cell clones expressing low surface densities of NCR (NCRdull) could lyse these tumors in an exclusively NKG2D-dependent fashion. Remarkably, not all of these targets expressed MICA/B, thus implying the existence of additional ligands recognized by NKG2D, possibly represented by GPI-linked molecules. Finally, we show that the engagement of different HLA class I-specific inhibitory receptors by either specific antibodies or the appropriate HLA class I ligand led to inhibition of NKG2D-mediated NK cell triggering.
KW - B
KW - MICA
KW - Natural cytotoxicity receptor
KW - Natural killer cell
KW - NKG2D
KW - Tumor cell lysis
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U2 - 10.1002/1521-4141(200104)31:4<1076::AID-IMMU1076>3.0.CO;2-Y
DO - 10.1002/1521-4141(200104)31:4<1076::AID-IMMU1076>3.0.CO;2-Y
M3 - Article
C2 - 11298332
AN - SCOPUS:0035054469
VL - 31
SP - 1076
EP - 1086
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 4
ER -