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Science 30 July 1999:
Vol. 285. no. 5428, pp. 727 - 729
DOI: 10.1126/science.285.5428.727

Reports

Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICA

Stefan Bauer, 1*dagger Veronika Groh, 1* Jun Wu, 2 Alexander Steinle, 1 Joseph H. Phillips, 2 Lewis L. Lanier, 2 Thomas Spies 1ddagger

Stress-inducible MICA, a distant homolog of major histocompatibility complex (MHC) class I, functions as an antigen for gamma delta T cells and is frequently expressed in epithelial tumors. A receptor for MICA was detected on most gamma delta T cells, CD8+ alpha beta T cells, and natural killer (NK) cells and was identified as NKG2D. Effector cells from all these subsets could be stimulated by ligation of NKG2D. Engagement of NKG2D activated cytolytic responses of gamma delta T cells and NK cells against transfectants and epithelial tumor cells expressing MICA. These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses.

1 Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
2 DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
*   These authors contributed equally to this work and are listed in alphabetical order.

dagger    Present address: Technical University of Munich, Institute of Microbiology, Trogerstrasse 32, D-81675 Munich, Germany.

ddagger    To whom correspondence should be addressed. E-mail: tspies{at}fred.fhcrc.org


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BCR/ABL oncogene directly controls MHC class I chain-related molecule A expression in chronic myelogenous leukemia..
N. Boissel, D. Rea, V. Tieng, N. Dulphy, M. Brun, J.-M. Cayuela, P. Rousselot, R. Tamouza, P. Le Bouteiller, F.-X. Mahon, et al. (2006)
J. Immunol. 176, 5108-5116
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Homing and Function of Human Skin {gamma}{delta} T Cells and NK Cells: Relevance for Tumor Surveillance.
L. M. Ebert, S. Meuter, and B. Moser (2006)
J. Immunol. 176, 4331-4336
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Synergistic antitumor effects of immune cell-viral biotherapy..
S. H. Thorne, R. S. Negrin, and C. H. Contag (2006)
Science 311, 1780-1784
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Placenta-Derived Soluble MHC Class I Chain-Related Molecules Down-Regulate NKG2D Receptor on Peripheral Blood Mononuclear Cells during Human Pregnancy: A Possible Novel Immune Escape Mechanism for Fetal Survival.
L. Mincheva-Nilsson, O. Nagaeva, T. Chen, U. Stendahl, J. Antsiferova, I. Mogren, J. Hernestal, and V. Baranov (2006)
J. Immunol. 176, 3585-3592
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Enhanced killing of primary ovarian cancer by retargeting autologous cytokine-induced killer cells with bispecific antibodies: a preclinical study..
J. K. Chan, C. A. Hamilton, M. K. Cheung, M. Karimi, J. Baker, J. M. Gall, S. Schulz, S. H. Thorne, N. N. Teng, C. H. Contag, et al. (2006)
Clin. Cancer Res. 12, 1859-1867
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