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Interaction between nectin-1 and the human natural killer cell receptor CD96

Favoreel, Herman, Holmes, Veronica M., Maluquer de Motes, Carlos, Richards, Paige T., Roldan, Jessenia, Bhargava, Arjun K., Orange, Jordan S. and Krummenacher, Claude (2019) Interaction between nectin-1 and the human natural killer cell receptor CD96 PLOS ONE, 14 (2), e0212443. pp. 1-19.

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Abstract

Regulation of Natural Killer (NK) cell activity is achieved by the integration of both activating and inhibitory signals acquired at the immunological synapse with potential target cells. NK cells express paired receptors from the immunoglobulin family which share common ligands from the nectin family of adhesion molecules. The activating receptor CD226 (DNAM-1) binds to nectin-2 and CD155, which are also recognized by the inhibitory receptor TIGIT. The third receptor in this family is CD96, which is less well characterized and may have different functions in human and mouse models. Human CD96 interacts with CD155 and ligation of this receptor activates NK cells, while in mice the presence of CD96 correlates with decreased NK cell activation. Mouse CD96 also binds nectin-1, but the effect of this interaction has not yet been determined. Here we show that human nectin-1 directly interacts with CD96 in vitro. The binding site for CD96 is located on the nectin-1 V-domain, which comprises a canonical interface that is shared by nectins to promote cell adhesion. The affinity of nectin-1 for CD96 is lower than for other nectins such as nectin-3 and nectin-1 itself. However, the affinity of nectin-1 for CD96 is similar to its affinity for herpes simplex virus glycoprotein D (HSV gD), which binds the nectin-1 V-domain during virus entry. The affinity of human CD96 for nectin-1 is lower than for its known activating ligand CD155. We also found that human erythroleukemia K562 cells, which are commonly used as susceptible targets to assess NK cell cytotoxicity did not express nectin-1 on their surface and were resistant to HSV infection. When expressed in K562 cells, nectin-1-GFP accumulated at cell contacts and allowed HSV entry. Furthermore, overexpression of nectin-1-GFP led to an increased susceptibility of K562 cells to NK-92 cell cytotoxicity.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine
Authors :
NameEmailORCID
Favoreel, Herman
Holmes, Veronica M.
Maluquer de Motes, Carlosc.maluquerdemotes@surrey.ac.uk
Richards, Paige T.
Roldan, Jessenia
Bhargava, Arjun K.
Orange, Jordan S.
Krummenacher, Claude
Date : 13 February 2019
Funders : Public Health Service, National Institute of Allergy and Infectious Diseases, College of Sciences and Mathematics at Rowan University
DOI : 10.1371/journal.pone.0212443
Copyright Disclaimer : © 2019 Holmes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Clive Harris
Date Deposited : 30 Sep 2019 13:01
Last Modified : 30 Sep 2019 13:01
URI: http://epubs.surrey.ac.uk/id/eprint/852837

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