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

RESEARCH ARTICLES

Confinement of Activating Receptors at the Plasma Membrane Controls Natural Killer Cell Tolerance

Sophie Guia1,2,3*, Baptiste N. Jaeger1,2,3*, Stefan Piatek1,2,3, Sébastien Mailfert1,2,3, Tomasz Trombik1,2,3, Aurore Fenis1,2,3, Nicolas Chevrier1,2,3{dagger}, Thierry Walzer1,2,3{ddagger}, Yann M. Kerdiles1,2,3, Didier Marguet1,2,3, Eric Vivier1,2,3,4§, and Sophie Ugolini1,2,3§

1 Centre d’Immunologie de Marseille-Luminy, Université de la Méditerranée, Campus de Luminy case 906, 13288 Marseille, France.
2 INSERM U631, 13288 Marseille, France.
3 CNRS, UMR6102, 13288 Marseille, France.
4 Assistance Publique–Hôpitaux de Marseille, Hôpital de la Conception, 13385 Marseille, France.

* These authors contributed equally to this work.

{dagger} Present address: Graduate Program in Immunology, Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA.

{ddagger} Present address: Université de Lyon, INSERM U851, 21 avenue Tony Garnier, Lyon F-69007, France.

Abstract: Natural killer (NK) cell tolerance to self is partly ensured by major histocompatibility complex (MHC) class I–specific inhibitory receptors on NK cells, which dampen their reactivity when engaged. However, NK cells that do not detect self MHC class I are not autoreactive. We used dynamic fluorescence correlation spectroscopy to show that MHC class I–independent NK cell tolerance in mice was associated with the presence of hyporesponsive NK cells in which both activating and inhibitory receptors were confined in an actin meshwork at the plasma membrane. In contrast, the recognition of self MHC class I by inhibitory receptors "educated" NK cells to become fully reactive, and activating NK cell receptors became dynamically compartmentalized in membrane nanodomains. We propose that the confinement of activating receptors at the plasma membrane is pivotal to ensuring the self-tolerance of NK cells.

§ To whom correspondence should be addressed. E-mail: ugolini{at}ciml.univ-mrs.fr (S.U.); vivier{at}ciml.univ-mrs.fr (E.V.)

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).

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