An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania
Journal article
Loh, Liyen, Saunders, Philippa M., Faoro, Camilla, Font-Porterias, Neus, Nemat-Gorgani, Neda, Harrison, Genelle F., Sadeeq, Suraju, Hensen, Luca, Wong, Shu Cheng, Widjaja, Jacqueline, Clemens, E. Bridie, Zhu, Shiying, Kichula, Katherine M., Tao, Sudan, Zhu, Faming, Montero-Martin, Gonzalo, Fernandez-Vina, Marcelo, Guethlein, Lisbeth A., Vivian, Julian P., ... Norman, Paul J.. (2024). An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania. Cell. 187(24), pp. 7008-7024. https://doi.org/10.1016/j.cell.2024.10.005
Authors | Loh, Liyen, Saunders, Philippa M., Faoro, Camilla, Font-Porterias, Neus, Nemat-Gorgani, Neda, Harrison, Genelle F., Sadeeq, Suraju, Hensen, Luca, Wong, Shu Cheng, Widjaja, Jacqueline, Clemens, E. Bridie, Zhu, Shiying, Kichula, Katherine M., Tao, Sudan, Zhu, Faming, Montero-Martin, Gonzalo, Fernandez-Vina, Marcelo, Guethlein, Lisbeth A., Vivian, Julian P., Davies, Jane, Mentzer, Alexander J., Oppenheimer, Stephen J., Pomat, William, Ioannidis, Alexander G., Barberena-Jonas, Carmina, Oceanian Genome Variation Project Consortium, Moreno-Estrada, Andrés, Miller, Adrian, Parham, Peter, Rossjohn, Jamie, Tong, Steven Y. C., Kedzierska, Katherine, Brooks, Andrew G. and Norman, Paul J. |
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Abstract | Genetic variation in host immunity impacts the disproportionate burden of infectious diseases that can be experienced by First Nations peoples. Polymorphic human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptors (KIRs) are key regulators of natural killer (NK) cells, which mediate early infection control. How this variation impacts their responses across populations is unclear. We show that HLA-A∗24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1∗114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1∗114+NK cells from First Nations Australian donors are inhibited through binding HLA-A∗24:02. The KIR3DL1∗114 lineage is defined by phenylalanine at residue 166. Structural and binding studies show phenylalanine 166 forms multiple unique contacts with HLA-peptide complexes, increasing both affinity and specificity. Accordingly, assessing immunogenetic variation and the functional implications for immunity are fundamental toward understanding population-based disease associations. |
Year | 2024 |
Journal | Cell |
Journal citation | 187 (24), pp. 7008-7024 |
Publisher | Cell Press |
ISSN | 0092-8674 |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.cell.2024.10.005 |
PubMed ID | 39476840 |
Scopus EID | 2-s2.0-85209832524 |
PubMed Central ID | PMC11606752 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 7008-7024 |
Funder | Australian Research Council (ARC) |
National Health and Medical Research Council (NHMRC) | |
National Institutes of Health (NIH), United States of America | |
Victorian Cancer Agency | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 27 Nov 2024 |
Publication process dates | |
Accepted | 03 Oct 2024 |
Deposited | 03 Apr 2025 |
Supplemental file | License File Access Level Open |
ARC Funded Research | This output has been funded, wholly or partially, under the Australian Research Council Act 2001 |
Grant ID | DP190103282 |
1042662 | |
1122524 | |
1145033 | |
R01 AI17892 | |
R01 AI151549 | |
1173871 | |
1091516 | |
P30 DK116073 | |
Additional information | © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
https://acuresearchbank.acu.edu.au/item/918z6/an-archaic-hla-class-i-receptor-allele-diversifies-natural-killer-cell-driven-immunity-in-first-nations-peoples-of-oceania
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Publisher's version
OA_Loh_2024_An_archaic_HLA_class_I_receptor.pdf | |
License: CC BY-NC-ND 4.0 | |
File access level: Open |
Supplemental file
OA_Loh_2024_An_archaic_HLA_class_I_receptor_[GRAPHICAL_ABSTRACT].jpg | |
License: CC BY-NC-ND 4.0 | |
File access level: Open |
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