title: Confinement of activating receptors at the plasma membrane controls natural killer cell tolerance.
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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Campus de Luminy, Marseille, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Guia
authors.forename: Baptiste N
authors.initials: BN
authors.lastname: Jaeger
authors.forename: Stefan
authors.initials: S
authors.lastname: Piatek
authors.forename: Sébastien
authors.initials: S
authors.lastname: Mailfert
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trombik
authors.forename: Aurore
authors.initials: A
authors.lastname: Fenis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chevrier
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.forename: Yann M
authors.initials: YM
authors.lastname: Kerdiles
authors.forename: Didier
authors.initials: D
authors.lastname: Marguet
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D017634:Self Tolerance / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013050:Spectrometry, Fluorescence
chemical_list: D000199:Actins; D017931:DNA Primers; D007371:Interferon-gamma; D002118:Calcium