High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.
View / Open Files
Authors
Huhn, Oisin
Retière, Christelle
Norman, Paul J
Jayaraman, Jyothi
Ito, Mitsutero
Parham, Peter
Ghadially, Hormas
Publication Date
2018-11-01Journal Title
J Immunol
ISSN
0022-1767
Publisher
The American Association of Immunologists
Volume
201
Issue
9
Pages
2593-2601
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Huhn, O., Chazara, O., Ivarsson, M. A., Retière, C., Venkatesan, T. C., Norman, P. J., Hilton, H. G., et al. (2018). High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.. J Immunol, 201 (9), 2593-2601. https://doi.org/10.4049/jimmunol.1800860
Abstract
Killer-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.
Keywords
Killer Cells, Natural, Cell Line, Humans, Pre-Eclampsia, Genetic Predisposition to Disease, Antibodies, Monoclonal, Flow Cytometry, Case-Control Studies, Pregnancy, Haplotypes, Alleles, Female, Receptors, KIR2DL1
Sponsorship
This 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.
Funder references
Medical Research Council (MR/P001092/1)
Wellcome Trust (200841/Z/16/Z)
Medical Research Council (G0901682)
European Research Council (695551)
Embargo Lift Date
2100-01-01
Identifiers
External DOI: https://doi.org/10.4049/jimmunol.1800860
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285151
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.