Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D

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Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D. / Pageon, Sophie V.; Cordoba, Shaun-Paul; Owen, Dylan M.; Rothery, Stephen M.; Oszmiana, Anna; Davis, Daniel M.

In: Science signaling, Vol. 6, No. 285, 23.07.2013.

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Pageon, Sophie V. ; Cordoba, Shaun-Paul ; Owen, Dylan M. ; Rothery, Stephen M. ; Oszmiana, Anna ; Davis, Daniel M. / Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D. In: Science signaling. 2013 ; Vol. 6, No. 285.

Bibtex

@article{963719af82934a48930e92f1d42ee92c,
title = "Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D",
abstract = "Natural killer (NK) cell responses are regulated by a dynamic equilibrium between activating and inhibitory receptor signals at the immune synapse (or interface) with target cells. Although the organization of receptors at the immune synapse is important for appropriate integration of these signals, there is little understanding of this in detail, because research has been hampered by the limited resolution of light microscopy. Through the use of superresolution single-molecule fluorescence microscopy to reveal the organization of the NK cell surface at the single-protein level, we report that the inhibitory receptor KIR2DL1 is organized in nanometer-scale clusters at the surface of human resting NK cells. Nanoclusters of KIR2DL1 became smaller and denser upon engagement of the activating receptor NKG2D, establishing an unexpected crosstalk between activating receptor signals and the positioning of inhibitory receptors. These rearrangements in the nanoscale organization of surface NK cell receptors were dependent on the actin cytoskeleton. Together, these data establish that NK cell activation involves a nanometer-scale reorganization of surface receptors, which in turn affects models for signal integration and thresholds that control NK cell effector functions and NK cell development.",
keywords = "LEUKOCYTE ANTIGEN-C, IMMUNE SYNAPSES, IMMUNOLOGICAL SYNAPSE, TARGET-CELLS, HLA-C, CYTOLYTIC INTERACTIONS, OPTICAL TWEEZERS, MOLECULES, SURFACE, ORGANIZATION",
author = "Pageon, {Sophie V.} and Shaun-Paul Cordoba and Owen, {Dylan M.} and Rothery, {Stephen M.} and Anna Oszmiana and Davis, {Daniel M.}",
year = "2013",
month = jul
day = "23",
doi = "10.1126/scisignal.2003947",
language = "English",
volume = "6",
journal = "Science signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "285",

}

RIS

TY - JOUR

T1 - Superresolution Microscopy Reveals Nanometer-Scale Reorganization of Inhibitory Natural Killer Cell Receptors upon Activation of NKG2D

AU - Pageon, Sophie V.

AU - Cordoba, Shaun-Paul

AU - Owen, Dylan M.

AU - Rothery, Stephen M.

AU - Oszmiana, Anna

AU - Davis, Daniel M.

PY - 2013/7/23

Y1 - 2013/7/23

N2 - Natural killer (NK) cell responses are regulated by a dynamic equilibrium between activating and inhibitory receptor signals at the immune synapse (or interface) with target cells. Although the organization of receptors at the immune synapse is important for appropriate integration of these signals, there is little understanding of this in detail, because research has been hampered by the limited resolution of light microscopy. Through the use of superresolution single-molecule fluorescence microscopy to reveal the organization of the NK cell surface at the single-protein level, we report that the inhibitory receptor KIR2DL1 is organized in nanometer-scale clusters at the surface of human resting NK cells. Nanoclusters of KIR2DL1 became smaller and denser upon engagement of the activating receptor NKG2D, establishing an unexpected crosstalk between activating receptor signals and the positioning of inhibitory receptors. These rearrangements in the nanoscale organization of surface NK cell receptors were dependent on the actin cytoskeleton. Together, these data establish that NK cell activation involves a nanometer-scale reorganization of surface receptors, which in turn affects models for signal integration and thresholds that control NK cell effector functions and NK cell development.

AB - Natural killer (NK) cell responses are regulated by a dynamic equilibrium between activating and inhibitory receptor signals at the immune synapse (or interface) with target cells. Although the organization of receptors at the immune synapse is important for appropriate integration of these signals, there is little understanding of this in detail, because research has been hampered by the limited resolution of light microscopy. Through the use of superresolution single-molecule fluorescence microscopy to reveal the organization of the NK cell surface at the single-protein level, we report that the inhibitory receptor KIR2DL1 is organized in nanometer-scale clusters at the surface of human resting NK cells. Nanoclusters of KIR2DL1 became smaller and denser upon engagement of the activating receptor NKG2D, establishing an unexpected crosstalk between activating receptor signals and the positioning of inhibitory receptors. These rearrangements in the nanoscale organization of surface NK cell receptors were dependent on the actin cytoskeleton. Together, these data establish that NK cell activation involves a nanometer-scale reorganization of surface receptors, which in turn affects models for signal integration and thresholds that control NK cell effector functions and NK cell development.

KW - LEUKOCYTE ANTIGEN-C

KW - IMMUNE SYNAPSES

KW - IMMUNOLOGICAL SYNAPSE

KW - TARGET-CELLS

KW - HLA-C

KW - CYTOLYTIC INTERACTIONS

KW - OPTICAL TWEEZERS

KW - MOLECULES

KW - SURFACE

KW - ORGANIZATION

U2 - 10.1126/scisignal.2003947

DO - 10.1126/scisignal.2003947

M3 - Article

VL - 6

JO - Science signaling

JF - Science signaling

SN - 1945-0877

IS - 285

ER -