Imperial College London
Alternate

Dr Becca Asquith

Faculty of Medicine, Department of Infectious Disease

Professor of Mathematical Immunology
 
 
 
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Contact

 

+44 (0)20 7594 3731b.asquith

 
 
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Location

 

112Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Nemat-Gorgani:2018:10.4049/jimmunol.1701780,
author = {Nemat-Gorgani, N and Hilton, HG and Henn, BM and Lin, M and Gignoux, CR and Myrick, JW and Werely, CJ and Granka, JM and Moller, M and Hoal, EG and Yawata, M and Yawata, N and Boelen, L and Asquith, RE and Parham, P and Norman, PJ},
doi = {10.4049/jimmunol.1701780},
journal = {Journal of Immunology},
title = {Different selected mechanisms attenuated the inhibitory interaction of KIR2DL1 with C2+ HLA-C in two indigenous human populations in Southern Africa},
url = {http://dx.doi.org/10.4049/jimmunol.1701780},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The functions of human NK cells in defense against pathogens and placental development during reproduction are modulated by interactions of killer cell Ig-like receptors (KIRs) with HLA-A, -B and -C class I ligands. Both receptors and ligands are highly polymorphic and exhibit extensive differences between human populations. Indigenous to southern Africa are the KhoeSan, the most ancient group of modern human populations, who have highest genomic diversity worldwide. We studied two KhoeSan populations, the Nama pastoralists and the ≠Khomani San hunter-gatherers. Comprehensive next-generation sequence analysis of HLA-A, -B, and -C and all KIR genes identified 248 different KIR and 137 HLA class I, which assort into ∼200 haplotypes for each gene family. All 74 Nama and 78 ≠Khomani San studied have different genotypes. Numerous novel KIR alleles were identified, including three arising by intergenic recombination. On average, KhoeSan individuals have seven to eight pairs of interacting KIR and HLA class I ligands, the highest diversity and divergence of polymorphic NK cell receptors and ligands observed to date. In this context of high genetic diversity, both the Nama and the ≠Khomani San have an unusually conserved, centromeric KIR haplotype that has arisen to high frequency and is different in the two KhoeSan populations. Distinguishing these haplotypes are independent mutations in KIR2DL1, which both prevent KIR2DL1 from functioning as an inhibitory receptor for C2+ HLA-C. The relatively high frequency of C2+ HLA-C in the Nama and the ≠Khomani San appears to have led to natural selection against strong inhibitory C2-specific KIR.
AU  - Nemat-Gorgani,N
AU  - Hilton,HG
AU  - Henn,BM
AU  - Lin,M
AU  - Gignoux,CR
AU  - Myrick,JW
AU  - Werely,CJ
AU  - Granka,JM
AU  - Moller,M
AU  - Hoal,EG
AU  - Yawata,M
AU  - Yawata,N
AU  - Boelen,L
AU  - Asquith,RE
AU  - Parham,P
AU  - Norman,PJ
DO  - 10.4049/jimmunol.1701780
PY  - 2018///
SN  - 1550-6606
TI  - Different selected mechanisms attenuated the inhibitory interaction of KIR2DL1 with C2+ HLA-C in two indigenous human populations in Southern Africa
T2  - Journal of Immunology
UR  - http://dx.doi.org/10.4049/jimmunol.1701780
ER  -
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