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...

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主要な著者: 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
フォーマット: Journal article
言語:English
出版事項: Public Library of Science 2010
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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.
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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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