Peptide-specific engagement of the activating NK cell receptor KIR2DS1

Abstract The activating NK cell receptor KIR2DS1 has been shown to be involved in many disorders including autoimmune diseases, malignancies and pregnancy outcomes. However, the precise ligands and functions of this receptor remain unclear. We aimed to gain a better understanding of the factors invo...

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Autores principales:	Anaïs Chapel, Wilfredo F. Garcia-Beltran, Angelique Hölzemer, Maja Ziegler, Sebastian Lunemann, Gloria Martrus, Marcus Altfeld
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3a5085e41caa41e8b81a476f571ddaf4
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spelling	oai:doaj.org-article:3a5085e41caa41e8b81a476f571ddaf42021-12-02T12:30:51ZPeptide-specific engagement of the activating NK cell receptor KIR2DS110.1038/s41598-017-02449-x2045-2322https://doaj.org/article/3a5085e41caa41e8b81a476f571ddaf42017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02449-xhttps://doaj.org/toc/2045-2322Abstract The activating NK cell receptor KIR2DS1 has been shown to be involved in many disorders including autoimmune diseases, malignancies and pregnancy outcomes. However, the precise ligands and functions of this receptor remain unclear. We aimed to gain a better understanding of the factors involved in the binding of KIR2DS1 and its inhibitory counterpart KIR2DL1 to HLA class I molecules, and the consequences for KIR2DS1+ NK-cell function. A systematic screen that assessed binding to 97 HLA-I proteins confirmed that KIR2DS1-binding was narrowly restricted to HLA-C group 2 complexes, while KIR2DL1 showed a broader binding specificity. Using KIR2DS1ζ+ Jurkat reporter-cells and peptide-pulsed 721.221.TAP1KO-HLA-C06:02 cells, we identified the synthetic peptide SRGPVHHLL presented by HLA-C06:02 that strongly engaged KIR2DS1- and KIR2DL1-binding. Functional analysis showed that this HLA-C*06:02-presented peptide can furthermore activate primary KIR2DS1(+) NK cell clones. Thus, we demonstrated peptide-dependent binding of the activating NK cell receptor KIR2DS1, providing new insights into the underlying mechanisms involved in KIR2DS1-related disorders.Anaïs ChapelWilfredo F. Garcia-BeltranAngelique HölzemerMaja ZieglerSebastian LunemannGloria MartrusMarcus AltfeldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anaïs Chapel Wilfredo F. Garcia-Beltran Angelique Hölzemer Maja Ziegler Sebastian Lunemann Gloria Martrus Marcus Altfeld Peptide-specific engagement of the activating NK cell receptor KIR2DS1
description	Abstract The activating NK cell receptor KIR2DS1 has been shown to be involved in many disorders including autoimmune diseases, malignancies and pregnancy outcomes. However, the precise ligands and functions of this receptor remain unclear. We aimed to gain a better understanding of the factors involved in the binding of KIR2DS1 and its inhibitory counterpart KIR2DL1 to HLA class I molecules, and the consequences for KIR2DS1+ NK-cell function. A systematic screen that assessed binding to 97 HLA-I proteins confirmed that KIR2DS1-binding was narrowly restricted to HLA-C group 2 complexes, while KIR2DL1 showed a broader binding specificity. Using KIR2DS1ζ+ Jurkat reporter-cells and peptide-pulsed 721.221.TAP1KO-HLA-C06:02 cells, we identified the synthetic peptide SRGPVHHLL presented by HLA-C06:02 that strongly engaged KIR2DS1- and KIR2DL1-binding. Functional analysis showed that this HLA-C*06:02-presented peptide can furthermore activate primary KIR2DS1(+) NK cell clones. Thus, we demonstrated peptide-dependent binding of the activating NK cell receptor KIR2DS1, providing new insights into the underlying mechanisms involved in KIR2DS1-related disorders.
format	article
author	Anaïs Chapel Wilfredo F. Garcia-Beltran Angelique Hölzemer Maja Ziegler Sebastian Lunemann Gloria Martrus Marcus Altfeld
author_facet	Anaïs Chapel Wilfredo F. Garcia-Beltran Angelique Hölzemer Maja Ziegler Sebastian Lunemann Gloria Martrus Marcus Altfeld
author_sort	Anaïs Chapel
title	Peptide-specific engagement of the activating NK cell receptor KIR2DS1
title_short	Peptide-specific engagement of the activating NK cell receptor KIR2DS1
title_full	Peptide-specific engagement of the activating NK cell receptor KIR2DS1
title_fullStr	Peptide-specific engagement of the activating NK cell receptor KIR2DS1
title_full_unstemmed	Peptide-specific engagement of the activating NK cell receptor KIR2DS1
title_sort	peptide-specific engagement of the activating nk cell receptor kir2ds1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3a5085e41caa41e8b81a476f571ddaf4
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Peptide-specific engagement of the activating NK cell receptor KIR2DS1

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