| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Molecular Biology,
Biomolecular Screening,
Protein Chemistry, and
Immunobiology, Immunex, Seattle, WA 98101
The UL16-binding proteins (ULBPs) are a novel family of MHC class
I-related molecules that were identified as targets of the human CMV
glycoprotein, UL16. We have previously shown that ULBP expression
renders a relatively resistant target cell sensitive to NK
cytotoxicity, presumably by engaging NKG2D, an activating receptor
expressed by NK and other immune effector cells. In this study we show
that NKG2D is the ULBP counterstructure on primary NK cells and that
its expression is up-regulated by IL-15 stimulation. Soluble forms of
ULBPs induce marked protein tyrosine phosphorylation, and activation of
the Janus kinase 2, STAT5, extracellular signal-regulated kinase,
mitogen-activated protein kinase, and phosphatidylinositol 3-kinase (PI
3-kinase)/Akt signal transduction pathways. ULBP-induced activation of
Akt and extracellular signal-regulated kinase and ULBP-induced IFN-
production are blocked by inhibitors of PI 3-kinase, consistent with
the known binding of PI 3-kinase to DAP10, the membrane-bound
signal-transducing subunit of the NKG2D receptor. While all three ULBPs
activate the same signaling pathways, ULBP3 was found to bind weakly
and to induce the weakest signal. In summary, we have shown that NKG2D
is the ULBP counterstructure on primary NK cells and for the first time
have identified signaling pathways that are activated by NKG2D ligands.
These results increase our understanding of the mechanisms by which
NKG2D activates immune effector cells and may have implications for
immune surveillance against pathogens and tumors.
This article has been cited by other articles:
|
|
 |
|
  M.-N. Peraldi, J. Berrou, N. Dulphy, A. Seidowsky, P. Haas, N. Boissel, F. Metivier, C. Randoux, N. Kossari, A. Guerin, et al. Oxidative Stress Mediates a Reduced Expression of the Activating Receptor NKG2D in NK Cells from End-Stage Renal Disease Patients J. Immunol., February 1, 2009; 182(3): 1696 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kumar, J. Hosse, C. von Toerne, E. Noessner, and P. J. Nelson JNK MAPK Pathway Regulates Constitutive Transcription of CCL5 by Human NK Cells through SP1 J. Immunol., January 15, 2009; 182(2): 1011 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Apps, L. Gardner, J. Traherne, V. Male, and A. Moffett Natural-killer cell ligands at the maternal-fetal interface: UL-16 binding proteins, MHC class-I chain related molecules, HLA-F and CD48 Hum. Reprod., November 1, 2008; 23(11): 2535 - 2548. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Cao, X. Xi, Z. Wang, L. Dong, Z. Hao, L. Cui, C. Ma, and W. He Four novel ULBP splice variants are ligands for human NKG2D Int. Immunol., August 1, 2008; 20(8): 981 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dulphy, P. Haas, M. Busson, S. Belhadj, R. Peffault de Latour, M. Robin, M. Carmagnat, P. Loiseau, R. Tamouza, C. Scieux, et al. An Unusual CD56brightCD16low NK Cell Subset Dominates the Early Posttransplant Period following HLA-Matched Hematopoietic Stem Cell Transplantation J. Immunol., August 1, 2008; 181(3): 2227 - 2237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Le Maux Chansac, D. Misse, C. Richon, I. Vergnon, M. Kubin, J.-C. Soria, A. Moretta, S. Chouaib, and F. Mami-Chouaib Potentiation of NK cell-mediated cytotoxicity in human lung adenocarcinoma: role of NKG2D-dependent pathway Int. Immunol., July 1, 2008; 20(7): 801 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Shriner, T. M. Baye, M. A. Padilla, S. Zhang, L. K. Vaughan, and A. E. Loraine Commonality of functional annotation: a method for prioritization of candidate genes from genome-wide linkage studies Nucleic Acids Res., March 27, 2008; 36(4): e26 - e26. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, B. Ge, M. Nicotra, J. N. H. Stern, H. D. Kopcow, X. Chen, and J. L. Strominger JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity PNAS, February 26, 2008; 105(8): 3017 - 3022. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Diermayr, H. Himmelreich, B. Durovic, A. Mathys-Schneeberger, U. Siegler, U. Langenkamp, J. Hofsteenge, A. Gratwohl, A. Tichelli, M. Paluszewska, et al. NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK-cell lines with single KIR-HLA class I specificities Blood, February 1, 2008; 111(3): 1428 - 1436. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Giurisato, M. Cella, T. Takai, T. Kurosaki, Y. Feng, G. D. Longmore, M. Colonna, and A. S. Shaw Phosphatidylinositol 3-Kinase Activation Is Required To Form the NKG2D Immunological Synapse Mol. Cell. Biol., December 15, 2007; 27(24): 8583 - 8599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Maccalli, D. Nonaka, A. Piris, D. Pende, L. Rivoltini, C. Castelli, and G. Parmiani NKG2D-Mediated Antitumor Activity by Tumor-Infiltrating Lymphocytes and Antigen-Specific T-Cell Clones Isolated from Melanoma Patients Clin. Cancer Res., December 15, 2007; 13(24): 7459 - 7468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Ostberg, B. E. Dayanc, M. Yuan, E. Oflazoglu, and E. A. Repasky Enhancement of natural killer (NK) cell cytotoxicity by fever-range thermal stress is dependent on NKG2D function and is associated with plasma membrane NKG2D clustering and increased expression of MICA on target cells J. Leukoc. Biol., November 1, 2007; 82(5): 1322 - 1331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Girart, M. B. Fuertes, C. I. Domaica, L. E. Rossi, and N. W. Zwirner Engagement of TLR3, TLR7, and NKG2D Regulate IFN-{gamma} Secretion but Not NKG2D-Mediated Cytotoxicity by Human NK Cells Stimulated with Suboptimal Doses of IL-12 J. Immunol., September 15, 2007; 179(6): 3472 - 3479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Malarkannan, J. Regunathan, H. Chu, S. Kutlesa, Y. Chen, H. Zeng, R. Wen, and D. Wang Bcl10 Plays a Divergent Role in NK Cell-Mediated Cytotoxicity and Cytokine Generation J. Immunol., September 15, 2007; 179(6): 3752 - 3762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Porcu-Buisson, M. Lambert, L. Lyonnet, A. Loundou, M. Gamerre, L. Camoin-Jau, F. Dignat-George, S. Caillat-Zucman, and P. Paul Soluble MHC Class I chain-related molecule serum levels are predictive markers of implantation failure and successful term pregnancies following IVF Hum. Reprod., August 1, 2007; 22(8): 2261 - 2266. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Cao, X. Xi, Z. Hao, W. Li, Y. Kong, L. Cui, C. Ma, D. Ba, and W. He RAET1E2, a Soluble Isoform of the UL16-binding Protein RAET1E Produced by Tumor Cells, Inhibits NKG2D-mediated NK Cytotoxicity J. Biol. Chem., June 29, 2007; 282(26): 18922 - 18928. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Epling-Burnette, F. Bai, J. S. Painter, D. E. Rollison, H. R. Salih, M. Krusch, J. Zou, E. Ku, B. Zhong, D. Boulware, et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors Blood, June 1, 2007; 109(11): 4816 - 4824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Y. Pappworth, E. C. Wang, and M. Rowe The Switch from Latent to Productive Infection in Epstein-Barr Virus-Infected B Cells Is Associated with Sensitization to NK Cell Killing J. Virol., January 15, 2007; 81(2): 474 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Sutherland, B. Rabinovich, N. J. Chalupny, P. Brawand, R. Miller, and D. Cosman ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with enhancement by IL-15 Blood, August 15, 2006; 108(4): 1313 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Borchers, N. L. Harris, S. C. Wesselkamper, M. Vitucci, and D. Cosman NKG2D ligands are expressed on stressed human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L222 - L231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. P. von Strandmann, H. P. Hansen, K. S. Reiners, R. Schnell, P. Borchmann, S. Merkert, V. R. Simhadri, A. Draube, M. Reiser, I. Purr, et al. A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo Blood, March 1, 2006; 107(5): 1955 - 1962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hanaoka, T. Kawaguchi, K. Horikawa, S. Nagakura, H. Mitsuya, and H. Nakakuma Immunoselection by natural killer cells of PIGA mutant cells missing stress-inducible ULBP Blood, February 1, 2006; 107(3): 1184 - 1191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Iannello, O. Debbeche, E. Martin, L. H. Attalah, S. Samarani, and A. Ahmad Viral strategies for evading antiviral cellular immune responses of the host J. Leukoc. Biol., January 1, 2006; 79(1): 16 - 35. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. T. Bryceson, M. E. March, H.-G. Ljunggren, and E. O. Long Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion Blood, January 1, 2006; 107(1): 159 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Markiewicz, L. N. Carayannopoulos, O. V. Naidenko, K. Matsui, W. R. Burack, E. L. Wise, D. H. Fremont, P. M. Allen, W. M. Yokoyama, M. Colonna, et al. Costimulation through NKG2D Enhances Murine CD8+ CTL Function: Similarities and Differences between NKG2D and CD28 Costimulation J. Immunol., September 1, 2005; 175(5): 2825 - 2833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rincon-Orozco, V. Kunzmann, P. Wrobel, D. Kabelitz, A. Steinle, and T. Herrmann Activation of V{gamma}9V{delta}2 T Cells by NKG2D J. Immunol., August 15, 2005; 175(4): 2144 - 2151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Wiemann, H.-W. Mittrucker, U. Feger, S. A. Welte, W. M. Yokoyama, T. Spies, H.-G. Rammensee, and A. Steinle Systemic NKG2D Down-Regulation Impairs NK and CD8 T Cell Responses In Vivo J. Immunol., July 15, 2005; 175(2): 720 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Nowbakht, M.-C. S. Ionescu, A. Rohner, C. P. Kalberer, E. Rossy, L. Mori, D. Cosman, G. De Libero, and A. Wodnar-Filipowicz Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias Blood, May 1, 2005; 105(9): 3615 - 3622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Smyth, J. Swann, J. M. Kelly, E. Cretney, W. M. Yokoyama, A. Diefenbach, T. J. Sayers, and Y. Hayakawa NKG2D Recognition and Perforin Effector Function Mediate Effective Cytokine Immunotherapy of Cancer J. Exp. Med., November 15, 2004; 200(10): 1325 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Vine, A. G. Heaps, L. Kaftantzi, A. Mosley, B. Asquith, A. Witkover, G. Thompson, M. Saito, P. K. C. Goon, L. Carr, et al. The Role of CTLs in Persistent Viral Infection: Cytolytic Gene Expression in CD8+ Lymphocytes Distinguishes between Individuals with a High or Low Proviral Load of Human T Cell Lymphotropic Virus Type 1 J. Immunol., October 15, 2004; 173(8): 5121 - 5129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. B. Rosen, M. Araki, J. A. Hamerman, T. Chen, T. Yamamura, and L. L. Lanier A Structural Basis for the Association of DAP12 with Mouse, but Not Human, NKG2D J. Immunol., August 15, 2004; 173(4): 2470 - 2478. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Siren, T. Sareneva, J. Pirhonen, M. Strengell, V. Veckman, I. Julkunen, and S. Matikainen Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages J. Gen. Virol., August 1, 2004; 85(8): 2357 - 2364. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Igarashi, J. Wynberg, R. Srinivasan, B. Becknell, J. P. McCoy Jr, Y. Takahashi, D. A. Suffredini, W. M. Linehan, M. A. Caligiuri, and R. W. Childs Enhanced cytotoxicity of allogeneic NK cells with killer immunoglobulin-like receptor ligand incompatibility against melanoma and renal cell carcinoma cells Blood, July 1, 2004; 104(1): 170 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Epling-Burnette, J. S. Painter, P. Chaurasia, F. Bai, S. Wei, J. Y. Djeu, and T. P. Loughran Jr Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes Blood, May 1, 2004; 103(9): 3431 - 3439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Friese, M. Platten, S. Z. Lutz, U. Naumann, S. Aulwurm, F. Bischof, H.-J. Buhring, J. Dichgans, H.-G. Rammensee, A. Steinle, et al. MICA/NKG2D-Mediated Immunogene Therapy of Experimental Gliomas Cancer Res., December 15, 2003; 63(24): 8996 - 9006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rolle, M. Mousavi-Jazi, M. Eriksson, J. Odeberg, C. Soderberg-Naucler, D. Cosman, K. Karre, and C. Cerboni Effects of Human Cytomegalovirus Infection on Ligands for the Activating NKG2D Receptor of NK Cells: Up-Regulation of UL16-Binding Protein (ULBP)1 and ULBP2 Is Counteracted by the Viral UL16 Protein J. Immunol., July 15, 2003; 171(2): 902 - 908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dunn, N. J. Chalupny, C. L. Sutherland, S. Dosch, P.V. Sivakumar, D. C. Johnson, and D. Cosman Human Cytomegalovirus Glycoprotein UL16 Causes Intracellular Sequestration of NKG2D Ligands, Protecting Against Natural Killer Cell Cytotoxicity J. Exp. Med., June 2, 2003; 197(11): 1427 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. T. A. K. Sindhu, R. Ahmad, R. Morisset, A. Ahmad, and J. Menezes Peripheral Blood Cytotoxic {gamma}{delta} T Lymphocytes from Patients with Human Immunodeficiency Virus Type 1 Infection and AIDS Lyse Uninfected CD4+ T Cells, and Their Cytocidal Potential Correlates with Viral Load J. Virol., February 1, 2003; 77(3): 1848 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pende, P. Rivera, S. Marcenaro, C.-C. Chang, R. Biassoni, R. Conte, M. Kubin, D. Cosman, S. Ferrone, L. Moretta, et al. Major Histocompatibility Complex Class I-related Chain A and UL16-Binding Protein Expression on Tumor Cell Lines of Different Histotypes: Analysis of Tumor Susceptibility to NKG2D-dependent Natural Killer Cell Cytotoxicity Cancer Res., November 1, 2002; 62(21): 6178 - 6186. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
