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High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.

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cam.issuedOnline2018-09-24
cam.orpheus.success2022/8/22
dc.contributor.authorHuhn, Oisín
dc.contributor.authorChazara, Olympe
dc.contributor.authorIvarsson, Martin A
dc.contributor.authorRetière, Christelle
dc.contributor.authorVenkatesan, Timothy C
dc.contributor.authorNorman, Paul J
dc.contributor.authorHilton, Hugo G
dc.contributor.authorJayaraman, Jyothi
dc.contributor.authorTraherne, James A
dc.contributor.authorTrowsdale, John
dc.contributor.authorIto, Mitsutero
dc.contributor.authorKling, Christiane
dc.contributor.authorParham, Peter
dc.contributor.authorGhadially, Hormas
dc.contributor.authorMoffett, Ashley
dc.contributor.authorSharkey, Andrew M
dc.contributor.authorColucci, Francesco
dc.contributor.orcidChazara, Olympe [0000-0003-0480-7808]
dc.contributor.orcidIvarsson, Martin A [0000-0002-7745-1331]
dc.contributor.orcidVenkatesan, Timothy C [0000-0002-7733-2308]
dc.contributor.orcidHilton, Hugo G [0000-0003-1488-7194]
dc.contributor.orcidTraherne, James A [0000-0002-6003-8559]
dc.contributor.orcidTrowsdale, John [0000-0002-0150-5698]
dc.contributor.orcidKling, Christiane [0000-0002-8809-9708]
dc.contributor.orcidMoffett, Ashley [0000-0002-8388-9073]
dc.contributor.orcidSharkey, Andrew M [0000-0002-5072-7748]
dc.contributor.orcidColucci, Francesco [0000-0001-5193-6376]
dc.date.accessioned2018-11-16T00:31:19Z
dc.date.available2018-11-16T00:31:19Z
dc.date.issued2018-11-01
dc.description.abstractKiller-cell Ig-like receptor (KIR) genes are inherited as haplotypes. They are expressed by NK cells and linked to outcomes of infectious diseases and pregnancy in humans. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family. Indeed, high-resolution KIR genotyping and phenotyping in single NK cells in the context of disease association is lacking. In this article, we describe a new method to separate NK cells expressing allotypes of the KIR2DL1 gene carried by the KIR A haplotype (KIR2DL1A) from those expressing KIR2DL1 alleles carried by the KIR B haplotype (KIR2DL1B). We find that in KIR AB heterozygous individuals, different KIR2DL1 allotypes can be detected in both peripheral blood and uterine NK cells. Using this new method, we demonstrate that both blood and uterine NK cells codominantly express KIR2DL1A and KIR2DL1B allotypes but with a predominance of KIR2DL1A variants, which associate with enhanced NK cell function. In a case-control study of pre-eclampsia, we show that KIR2DL1A, not KIR2DL1B, associates with increased disease risk. This method will facilitate our understanding of how individual KIR2DL1 allelic variants affect NK cell function and contribute to disease risk.
dc.description.sponsorshipThis work was funded by the Wellcome Trust (Grant 200841/Z/16/Z to FC and AM), the Medical Research Council (Grant MR/P001092/1 to AS), the National Institutes of Health (Grant NIH U01 AI090905 to PJN and R01 AI17892 to PP) and the Cambridge NIHR BRC Cell Phenotyping Hub (to FC). The POPS study is funded by the Women’s Health theme of the NIHR Cambridge Biomedical Research Centre and the Stillbirth and Neonatal Death Society (SANDS). OH was supported by a MedImmune-Cambridge PhD fellowship. OC was supported by a CTR Next Generation Fellowship.
dc.format.mediumPrint-Electronic
dc.identifier.doi10.17863/CAM.32521
dc.identifier.eissn1550-6606
dc.identifier.issn0022-1767
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/285151
dc.languageeng
dc.language.isoeng
dc.publisherThe American Association of Immunologists
dc.publisher.urlhttp://dx.doi.org/10.4049/jimmunol.1800860
dc.subjectAlleles
dc.subjectAntibodies, Monoclonal
dc.subjectCase-Control Studies
dc.subjectCell Line
dc.subjectFemale
dc.subjectFlow Cytometry
dc.subjectGenetic Predisposition to Disease
dc.subjectHaplotypes
dc.subjectHumans
dc.subjectKiller Cells, Natural
dc.subjectPre-Eclampsia
dc.subjectPregnancy
dc.subjectReceptors, KIR2DL1
dc.titleHigh-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.
dc.typeArticle
dcterms.dateAccepted2018-08-22
prism.endingPage2601
prism.issueIdentifier9
prism.publicationDate2018
prism.publicationNameJ Immunol
prism.startingPage2593
prism.volume201
pubs.funder-project-idMedical Research Council (MR/P001092/1)
pubs.funder-project-idWellcome Trust (200841/Z/16/Z)
pubs.funder-project-idMedical Research Council (G0901682)
pubs.funder-project-idEuropean Research Council (695551)
rioxxterms.licenseref.startdate2018-11
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.4049/jimmunol.1800860

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