TY - JOUR
T1 - Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity
AU - Le Bouteiller, Philippe
AU - Barakonyi, Aliz
AU - Giustiniani, Jérome
AU - Lenfant, Françoise
AU - Marie-Cardine, Anne
AU - Aguerre-Girr, Maryse
AU - Rabot, Magali
AU - Hilgert, Ivan
AU - Mami-Chouaib, Fathia
AU - Tabiasco, Julie
AU - Boumsell, Laurence
AU - Bensussan, Armand
PY - 2002/12/24
Y1 - 2002/12/24
N2 - Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class 1-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56áim+ NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94/CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160/HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.
AB - Circulating human natural killer (NK) lymphocytes have been functionally defined by their ability to exert cytotoxic activity against MHC class 1-negative target cell lines, including K562. Therefore, it was proposed that NK cells recognized the "missing self." We show here that the Ig-like CD160 receptor expressed by circulating CD56áim+ NK cells or IL-2-deprived NK cell lines is mainly involved in their cytotoxic activity against K562 target cells. Further, we report that HLA-C molecules that are constitutively expressed by K562 trigger NK cell lysis through CD160 receptor engagement. In addition, we demonstrate, with recombinant soluble HLA-Cw3 and CD160 proteins, direct interaction of these molecules. We also find that CD158b inhibitory receptors partially interfere with CD160-mediated cytotoxicity, whereas CD94/CD159a and CD85j have no effect on engagement with their respective ligands. Thus, CD160/HLA-C interaction constitutes a unique pathway to trigger NK cell cytotoxic activity.
KW - Activation
KW - HLA class
KW - NK receptors
UR - http://www.scopus.com/inward/record.url?scp=0037168611&partnerID=8YFLogxK
U2 - 10.1073/pnas.012681099
DO - 10.1073/pnas.012681099
M3 - Article
C2 - 12486241
AN - SCOPUS:0037168611
SN - 0027-8424
VL - 99
SP - 16963
EP - 16968
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -