Abstract
HLA class I molecules and killer cell immunoglobulin-like receptors (KIR) form a diverse system of ligands and receptors that individualize human immune systems in ways that improve the survival of individuals and populations. Human settlement of Oceania by island-hop** East and Southeast Asian migrants started ~3,500 years ago. Subsequently, New Zealand was reached ~750 years ago by ancestral Māori. To examine how this history impacted KIR and HLA diversity, and their functional interaction, we defined at high resolution the allelic and haplotype diversity of the 13 expressed KIR genes in 49 Māori and 34 Polynesians. Eighty KIR variants, including four ‘new’ alleles, were defined, as were 35 centromeric and 22 telomeric KIR region haplotypes, which combine to give >50 full-length KIR haplotypes. Two new and divergent variant KIR form part of a telomeric KIR haplotype, which appears derived from Papua New Guinea and was probably obtained by the Asian migrants en route to Polynesia. Māori and Polynesian KIR are very similar, but differ significantly from African, European, Japanese, and Amerindian KIR. Māori and Polynesians have high KIR haplotype diversity with corresponding allotype diversity being maintained throughout the KIR locus. Within the population, each individual has a unique combination of HLA class I and KIR. Characterizing Māori and Polynesians is a paucity of HLA-B allotypes recognized by KIR. Compensating for this deficiency are high frequencies (>50 %) of HLA-A allotypes recognized by KIR. These HLA-A allotypes are ones that modern humans likely acquired from archaic humans at a much earlier time.
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Acknowledgments
We thank Jyothi Jayaraman for technical assistance, Eric Long for advice, and Derek Middleton for use of genotype data. This study was supported by U.S. National Institutes of Health grants AI17892 (PP, PJN, NNG) and GM109030 (JAH, PJN, PP), the Medical Research Council of the UK (JAT), and by the Victoria University of Wellington, NZ, and Ministry of Higher Education, Malaysia.
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Supplementary Figure 1
Potential interactions of Māori and Polynesian HLA-A, HLA-B, and HLA-C with KIR. Shown in the two columns on the right of each panel are the frequencies of HLA-C (panel a), HLA-A (panel b), and HLA-B (panel c) allotypes in the Māori and Polynesians. In the central columns are shown the KIR that can recognize each allotype (PDF 15 kb)
Supplementary Figure 2
KIR allele frequencies in Māori and Polynesians. Shown are the KIR alleles and their frequencies in the Māori and Polynesian populations. KIR allotypes that are known or predicted to be unexpressed at the cell surface are given in red. Alleles of the centromeric KIR genes are given in panel a; alleles of the telomeric KIR genes are given in panel b (PDF 19 kb)
Supplementary Figure 3
Māori and Polynesian allotype-level KIR haplotypes. In the depiction on the left are shown the Māori and Polynesian centromeric (panel a) and telomeric (panel b) KIR haplotypes with only variation that alters protein sequence or expression being taken into account. Boxes corresponding to KIR A haplotypes are colored red, and KIR B haplotypes are colored blue. In the columns on the right, the frequency of each haplotype is compared with that in Amerindian, European, and sub-Saharan African populations that have also been studied at high resolution. (Gendzekhadze et al. 2009; Norman et al. 2013; Vierra-Green et al. 2012). The Japanese population (Yawata et al. 2006) was not fully typed for centromeric KIR, so only the telomeric segment is shown (PDF 22 kb)
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Nemat-Gorgani, N., Edinur, H.A., Hollenbach, J.A. et al. KIR diversity in Māori and Polynesians: populations in which HLA-B is not a significant KIR ligand. Immunogenetics 66, 597–611 (2014). https://doi.org/10.1007/s00251-014-0794-1
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DOI: https://doi.org/10.1007/s00251-014-0794-1