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Educated natural killer cells show dynamic movement of the activating receptor NKp46 and confinement of the inhibitory receptor Ly49A
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.ORCID iD: 0000-0002-4762-4887
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2018 (English)In: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 11, no 517, article id eaai9200Article in journal (Refereed) Published
Abstract [en]

Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education has so far not been fully described. In addition, distinctive phenotypic markers of educated NK cells at the single-cell level are lacking. We developed a refined version of the image mean square displacement (iMSD) method (called iMSD carpet analysis) and used it in combination with single-particle tracking to characterize the dynamics of the activating receptor NKp46 and the inhibitory receptor Ly49A on resting educated versus hyporesponsive murine NK cells. Most of the NKp46 and Ly49A molecules were restricted to microdomains; however, individual NKp46 molecules resided in these domains for shorter periods and diffused faster on the surface of educated, compared to hyporesponsive, NK cells. In contrast, the movement of Ly49A was more constrained in educated NK cells compared to hyporesponsive NK cells. Either disrupting the actin cytoskeleton or adding cholesterol to the cells prohibited activating signaling, suggesting that the dynamics of receptor movements within the cell membrane are critical for the proper activation of NK cells. The faster and more dynamic movement of NKp46 in educated NK cells may facilitate a swifter response to interactions with target cells.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2018. Vol. 11, no 517, article id eaai9200
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Medical Biotechnology
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URN: urn:nbn:se:kth:diva-223794DOI: 10.1126/scisignal.aai9200ISI: 000424982900001Scopus ID: 2-s2.0-85041966098OAI: oai:DiVA.org:kth-223794DiVA, id: diva2:1188271
Funder
Swedish Research CouncilMagnus Bergvall FoundationVINNOVANIH (National Institute of Health), P41-GM103540; P50-GM076516
Note

QC 20180307

Available from: 2018-03-07 Created: 2018-03-07 Last updated: 2018-03-07Bibliographically approved

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Piguet, Joachim

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