NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases

被引:148
作者
Zompi, S
Hamerman, JA
Ogasawara, K
Schweighoffer, E
Tybulewicz, VLJ
Di Santo, JP
Lanier, LL
Colucci, F
机构
[1] Inst Pasteur, Dept Immunol, F-75015 Paris, France
[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[3] Natl Inst Med Res, Div Immune Cell Biol, London NW7 1AA, England
关键词
D O I
10.1038/ni930
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In activated mouse natural killer (NK) cells, the NKG2D receptor associates with two intracellular adaptors, DAP10 and DAP12, which trigger phosphatidyl inositol 3 kinase (PI3K) and Syk family protein tyrosine kinases, respectively. Here we show that cytotoxicity, but not cytokine production, is triggered by NKG2D in activated NK cells lacking either DAP12 or the Syk family members Syk and ZAP70. Inhibition of PI3K blocks this cytotoxicity, suggesting that the DAP10-PI3K pathway is sufficient to initiate NKG2D-mediated killing of target cells. Our results highlight signaling divergence in the effector functions of NKG2D and indicate that alternative associations between a receptor and its adaptors may provide a single receptor with a dual 'on-switch', giving mouse NK cells more choices through which to trigger cytotoxicity.
引用
收藏
页码:565 / 572
页数:8
相关论文
共 39 条
[1]   Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors [J].
Arase, H ;
Mocarski, ES ;
Campbell, AE ;
Hill, AB ;
Lanier, LL .
SCIENCE, 2002, 296 (5571) :1323-1326
[2]   DAP12-deficient mice fail to develop autoimmunity due to impaired antigen priming [J].
Bakker, ABH ;
Hoek, RM ;
Cerwenka, A ;
Blom, B ;
Lucian, L ;
McNeil, T ;
Murray, R ;
Phillips, JH ;
Sedgwick, JD ;
Lanier, LL .
IMMUNITY, 2000, 13 (03) :345-353
[3]   Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA [J].
Bauer, Stefan ;
Groh, Veronika ;
Wu, Jun ;
Steinle, Alexander ;
Phillips, Joseph H. ;
Lanier, Lewis L. ;
Spies, Thomas .
JOURNAL OF IMMUNOLOGY, 2018, 200 (07) :2231-2233
[4]  
BILLADEAU DD, 2003, NAT IMMUNOL
[5]   Natural killer cells in antiviral defense: Function and regulation by innate cytokines [J].
Biron, CA ;
Nguyen, KB ;
Pien, GC ;
Cousens, LP ;
Salazar-Mather, TP .
ANNUAL REVIEW OF IMMUNOLOGY, 1999, 17 :189-220
[6]   Cutting edge: Murine UL16-binding protein-like transcript 1: A newly described transcript encoding a high-affinity ligand for marine NKG2D [J].
Carayannopoulos, LN ;
Naidenko, OV ;
Fremont, DH ;
Yokoyama, WM .
JOURNAL OF IMMUNOLOGY, 2002, 169 (08) :4079-4083
[7]   Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice [J].
Cerwenka, A ;
Bakker, ABH ;
McClanahan, T ;
Wagner, J ;
Wu, J ;
Phillips, JH ;
Lanier, LL .
IMMUNITY, 2000, 12 (06) :721-727
[8]   Ectopic expression of retinoic acid early inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a MHC class I-bearing tumor in vivo [J].
Cerwenka, A ;
Baron, JL ;
Lanier, LL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (20) :11521-11526
[9]   Ligands for natural killer cell receptors: redundancy or specificity [J].
Cerwenka, A ;
Lanier, LL .
IMMUNOLOGICAL REVIEWS, 2001, 181 :158-169
[10]   2B4 (CD244)-mediated activation of cytotoxicity and IFN-γ release in human NK cells involves distinct pathways [J].
Chuang, SS ;
Kumaresan, PR ;
Mathew, PA .
JOURNAL OF IMMUNOLOGY, 2001, 167 (11) :6210-6216