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A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner.
Sci Signal. 2018 04 10; 11(525)SS

Abstract

Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using superresolution microscopy, we found that NKG2D is constitutively arranged in nanoclusters at the surface of human primary NK cells. Nanoclusters of NKG2D became smaller upon ligation with MICA but became larger upon activation by ULBP2. In addition, ULBP2 induced the reorganization of nanoclusters of the cytokine receptor subunit for both interleukin-2 (IL-2) and IL-15 (IL-2/IL-15Rβ), such that these cytokine receptor subunits coalesced with nanoclusters of NKG2D. Functionally, the response of NK cells activated by ULBP2 was augmented by an interaction between ULBP2-bound NKG2D and IL-15R ligated by IL-15 (trans-presented by IL-15Rα-coated surfaces). These data suggest that NKG2DLs are not equivalent in their capacity to activate NKG2D and establish a previously unknown paradigm in how ligand-induced changes to the nanoscale organization of the cell surface can affect immune responses.

Authors+Show Affiliations

Manchester Collaborative Centre for Inflammation Research, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK.Manchester Collaborative Centre for Inflammation Research, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK.Manchester Collaborative Centre for Inflammation Research, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK. daniel.davis@manchester.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29636390

Citation

Bálint, Štefan, et al. "A Nanoscale Reorganization of the IL-15 Receptor Is Triggered By NKG2D in a Ligand-dependent Manner." Science Signaling, vol. 11, no. 525, 2018.
Bálint Š, Lopes FB, Davis DM. A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner. Sci Signal. 2018;11(525).
Bálint, Š., Lopes, F. B., & Davis, D. M. (2018). A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner. Science Signaling, 11(525). https://doi.org/10.1126/scisignal.aal3606
Bálint Š, Lopes FB, Davis DM. A Nanoscale Reorganization of the IL-15 Receptor Is Triggered By NKG2D in a Ligand-dependent Manner. Sci Signal. 2018 04 10;11(525) PubMed PMID: 29636390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A nanoscale reorganization of the IL-15 receptor is triggered by NKG2D in a ligand-dependent manner. AU - Bálint,Štefan, AU - Lopes,Filipa B, AU - Davis,Daniel M, Y1 - 2018/04/10/ PY - 2018/4/12/entrez PY - 2018/4/11/pubmed PY - 2019/9/17/medline JF - Science signaling JO - Sci Signal VL - 11 IS - 525 N2 - Natural killer group 2D (NKG2D), an activating receptor on natural killer (NK) cells and a subset of T cells, recognizes stress-inducible proteins, including MICA and ULBP2, which are present on infected or transformed cells. Whether each NKG2D ligand (NKG2DL) has a distinct biological role is not clear. Using superresolution microscopy, we found that NKG2D is constitutively arranged in nanoclusters at the surface of human primary NK cells. Nanoclusters of NKG2D became smaller upon ligation with MICA but became larger upon activation by ULBP2. In addition, ULBP2 induced the reorganization of nanoclusters of the cytokine receptor subunit for both interleukin-2 (IL-2) and IL-15 (IL-2/IL-15Rβ), such that these cytokine receptor subunits coalesced with nanoclusters of NKG2D. Functionally, the response of NK cells activated by ULBP2 was augmented by an interaction between ULBP2-bound NKG2D and IL-15R ligated by IL-15 (trans-presented by IL-15Rα-coated surfaces). These data suggest that NKG2DLs are not equivalent in their capacity to activate NKG2D and establish a previously unknown paradigm in how ligand-induced changes to the nanoscale organization of the cell surface can affect immune responses. SN - 1937-9145 UR - https://www.unboundmedicine.com/medline/citation/29636390/A_nanoscale_reorganization_of_the_IL_15_receptor_is_triggered_by_NKG2D_in_a_ligand_dependent_manner_ L2 - http://stke.sciencemag.org/cgi/pmidlookup?view=long&pmid=29636390 DB - PRIME DP - Unbound Medicine ER -