Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. Signal., 5 April 2011
Vol. 4, Issue 167, p. ra21
[DOI: 10.1126/scisignal.2001608]


Editor's Summary

Corralling Receptors
Coordination of the signaling of activating and inhibitory surface receptors determines the responsiveness of natural killer (NK) cells. The engagement of inhibitory receptors specific for self major histocompatibility complex (MHC) class I is critical to the "education" of NK cells so that they can recognize "self" and become competent effector cells. However, NK cells lacking such inhibitory receptors do not become autoreactive; instead, they become unresponsive to stimulation of their activating receptors. Guia et al. used fluorescence correlation spectroscopy to determine the membrane distribution of activating and inhibitory receptors in mouse NK cells that were either hyporesponsive or competent. This analysis revealed that in the absence of self MHC class I–specific inhibitory receptors, activating and other inhibitory receptors were confined to areas of membrane associated with an actin-rich meshwork. However, engagement of self MHC class I–specific inhibitory receptors triggered the movement of activating receptors out of the actin-rich region and into distinct membrane nanodomains that were more favorable for signaling. Thus, NK cells that fail to become educated remain unresponsive because of the confinement of their activating receptors.

Citation: S. Guia, B. N. Jaeger, S. Piatek, S. Mailfert, T. Trombik, A. Fenis, N. Chevrier, T. Walzer, Y. M. Kerdiles, D. Marguet, E. Vivier, S. Ugolini, Confinement of Activating Receptors at the Plasma Membrane Controls Natural Killer Cell Tolerance. Sci. Signal. 4, ra21 (2011).

Read the Full Text

T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow.
C. Daussy, F. Faure, K. Mayol, S. Viel, G. Gasteiger, E. Charrier, J. Bienvenu, T. Henry, E. Debien, U. A. Hasan, et al. (2014)
J. Exp. Med. 211, 563-577
   Abstract »    Full Text »    PDF »
A Genetic Defect in Mice That Impairs Missing Self Recognition Despite Evidence for Normal Maturation and MHC Class I-Dependent Education of NK Cells.
S. L. Wickstrom, L. Oberg, K. Karre, and M. H. Johansson (2014)
J. Immunol. 192, 1577-1586
   Abstract »    Full Text »    PDF »
Education of Murine NK Cells Requires Both cis and trans Recognition of MHC Class I Molecules.
S. Bessoles, G. S. Angelov, J. Back, G. Leclercq, E. Vivier, and W. Held (2013)
J. Immunol. 191, 5044-5051
   Abstract »    Full Text »    PDF »
Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D.
S. V. Pageon, S.-P. Cordoba, D. M. Owen, S. M. Rothery, A. Oszmiana, and D. M. Davis (2013)
Science Signaling 6, ra62
   Abstract »    Full Text »    PDF »
Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire.
S. Sheppard, C. Triulzi, M. Ardolino, D. Serna, L. Zhang, D. H. Raulet, and N. Guerra (2013)
Blood 121, 5025-5033
   Abstract »    Full Text »    PDF »
NK Cell Tolerance of Self-Specific Activating Receptor KIR2DS1 in Individuals with Cognate HLA-C2 Ligand.
G. Pittari, X.-R. Liu, A. Selvakumar, Z. Zhao, E. Merino, M. Huse, J. H. Chewning, K. C. Hsu, and B. Dupont (2013)
J. Immunol. 190, 4650-4660
   Abstract »    Full Text »    PDF »
MicroRNA-Deficient NK Cells Exhibit Decreased Survival but Enhanced Function.
R. P. Sullivan, J. W. Leong, S. E. Schneider, C. R. Keppel, E. Germino, A. R. French, and T. A. Fehniger (2012)
J. Immunol. 188, 3019-3030
   Abstract »    Full Text »    PDF »
Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis.
B. N. Jaeger, J. Donadieu, C. Cognet, C. Bernat, D. Ordonez-Rueda, V. Barlogis, N. Mahlaoui, A. Fenis, E. Narni-Mancinelli, B. Beaupain, et al. (2012)
J. Exp. Med. 209, 565-580
   Abstract »    Full Text »    PDF »
Natural Killer Cell Tolerance: Control by Self or Self-Control?.
B. N. Jaeger and E. Vivier (2012)
Cold Spring Harb Perspect Biol 4, a007229
   Abstract »    Full Text »    PDF »
Skewing of the NK Cell Repertoire by MHC Class I via Quantitatively Controlled Enrichment and Contraction of Specific Ly49 Subsets.
P. Brodin, T. Lakshmikanth, K. Karre, and P. Hoglund (2012)
J. Immunol. 188, 2218-2226
   Abstract »    Full Text »    PDF »
Integration of Activating and Inhibitory Receptor Signaling by Regulated Phosphorylation of Vav1 in Immune Cells.
S. Mesecke, D. Urlaub, H. Busch, R. Eils, and C. Watzl (2011)
Science Signaling 4, ra36
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 5 April 2011..
S. Ugolini, E. Vivier, and A. M. VanHook (2011)
Science Signaling 4, pc7
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882