Abstract
The role of natural killer (NK) cells is tightly modulated by interactions of killer cell immunoglobulin-like receptors (KIR) with their ligands of the MHC class I family. Several characteristics of the KIR gene products are conserved in primate evolution, like the receptor structures and the variegated expression pattern. At the genomic level, however, the clusters encoding the KIR family display species-specific diversity, reflected by differential gene expansions and haplotype architecture. The human KIR cluster is extensively studied in large cohorts from various populations, which revealed two KIR haplotype groups, A and B, that represent more inhibitory and more activating functional profiles, respectively. So far, genomic KIR analyses in large outbred populations of non-human primate species are lacking. In this study, we roughly quadrupled the number of rhesus macaques studied for their KIR transcriptome (n = 298). Using segregation analysis, we defined 112 unique KIR region configurations, half of which display a more inhibitory profile, whereas the other half has a more activating potential. The frequencies and functional potential of these profiles might mirror the human KIR haplotype groups. However, whereas the human group A and B KIR haplotypes are confined to largely fixed organizations, the haplotypes in macaques feature highly variable gene content. Moreover, KIR homozygosity was hardly encountered in this panel of macaques. This study exhibits highly diverse haplotype architectures in humans and macaques, which nevertheless might have an equivalent effect on the modulation of NK cell activity.
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Acknowledgements
We thank Prof. Dr. A. Sanchez-Mazas and Dr. J. M. Nunes from the Anthropology Unit of the Department of Genetics and Evolution (University of Geneva, Switzerland) for their advice on pairwise gene linkage analysis. We also thank D. Devine for editing the manuscript and F. van Hassel for preparing the figures.
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This work was supported in part by the NIH/NIAID contract number HHSN272201600007C.
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NdG and AdV-R performed all practical work. NdG, AdV-R, and JB analyzed the data. JB wrote the manuscript. NGdG and RB supervised the project and edited the manuscript.
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Bruijnesteijn, J., de Groot, N., de Vos-Rouweler, A.J.M. et al. Comparative genetics of KIR haplotype diversity in humans and rhesus macaques: the balancing act. Immunogenetics 74, 313–326 (2022). https://doi.org/10.1007/s00251-022-01259-4
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DOI: https://doi.org/10.1007/s00251-022-01259-4