Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells.
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human N...
主要な著者: | , , , , , , , , , , , , |
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フォーマット: | Journal article |
言語: | English |
出版事項: |
Public Library of Science
2010
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_version_ | 1826284230222544896 |
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author | Köhler, K Xiong, S Brzostek, J Mehrabi, M Eissmann, P Harrison, A Cordoba, S Oddos, S Miloserdov, V Gould, K Burroughs, N van der Merwe, P Davis, D |
author_facet | Köhler, K Xiong, S Brzostek, J Mehrabi, M Eissmann, P Harrison, A Cordoba, S Oddos, S Miloserdov, V Gould, K Burroughs, N van der Merwe, P Davis, D |
author_sort | Köhler, K |
collection | OXFORD |
description | It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions. |
first_indexed | 2024-03-07T01:10:45Z |
format | Journal article |
id | oxford-uuid:8cec9f15-3067-4848-b78f-c49c5f9f10cb |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T01:10:45Z |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | dspace |
spelling | oxford-uuid:8cec9f15-3067-4848-b78f-c49c5f9f10cb2022-03-26T22:47:47ZMatched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8cec9f15-3067-4848-b78f-c49c5f9f10cbEnglishSymplectic Elements at OxfordPublic Library of Science2010Köhler, KXiong, SBrzostek, JMehrabi, MEissmann, PHarrison, ACordoba, SOddos, SMiloserdov, VGould, KBurroughs, Nvan der Merwe, PDavis, DIt has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions. |
spellingShingle | Köhler, K Xiong, S Brzostek, J Mehrabi, M Eissmann, P Harrison, A Cordoba, S Oddos, S Miloserdov, V Gould, K Burroughs, N van der Merwe, P Davis, D Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title | Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title_full | Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title_fullStr | Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title_full_unstemmed | Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title_short | Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human natural killer cells. |
title_sort | matched sizes of activating and inhibitory receptor ligand pairs are required for optimal signal integration by human natural killer cells |
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