Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance.

Sophie Guia (1) , Baptiste N Jaeger (1) , Stefan Piatek (1) , Sébastien Mailfert (1) , Tomasz Trombik (1) , Aurore Fenis (1) , Nicolas Chevrier (1) , Thierry Walzer (1) , Yann M Kerdiles (1) , Didier Marguet (1) , Eric Vivier (1, 2) , Sophie Ugolini (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 Service de Chirurgie

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.

Domaines: Immunologie

Sophie Guia, Baptiste N Jaeger, Stefan Piatek, Sébastien Mailfert, Tomasz Trombik, et al.. Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance.. Science Signaling, 2011, 4 (167), pp.ra21. ⟨10.1126/scisignal.2001608⟩. ⟨hal-00609667⟩