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Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells

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Köhler, Karsten, Xiong, Shiqiu, Brzostek, Joanna, Mehrabi, Maryam, Eissmann, Philipp, Harrison, Alice, Cordoba, Shaun-Paul, Oddos, Stephane, Miloserdov, Vladimir, Gould, Keith, Burroughs, Nigel John, Van der Merwe, Philip Anton and Davis, Daniel M.. (2010) Matched sizes of activating and inhibitory receptor/ligand pairs are required for optimal signal integration by human Natural Killer cells. PL o S One, Vol.5 (No.11). e15374. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/journal.pone.0015374

Abstract

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.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Mathematics Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Receptor-ligand complexes, Killer cells
Journal or Publication Title:	PL o S One
Publisher:	Public Library of Science
ISSN:	1932-6203
Date:	5 November 2010
Volume:	Vol.5
Number:	No.11
Page Range:	e15374
Identification Number:	10.1371/journal.pone.0015374
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Royal Society (Great Britain), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Medical Research Council (Great Britain) (MRC)
Grant number:	BB/D011663/1 (BBSRC), G0500563 (MRC)
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URI:	http://wrap.warwick.ac.uk/id/eprint/3961