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An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania
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
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
Author
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.
Norman, Paul J.
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.
Norman, Paul J.
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.
Keywords
Date
2024
Type
Journal article
Journal
Cell
Book
Volume
187
Issue
24
Page Range
7008-7024
Article Number
ACU Department
Marketing and Communications
Research Office
Research Office
Collections
Relation URI
Source URL
Event URL
Open Access Status
Published as ‘gold’ (paid) open access
License
File Access
Open
Open
Open
Notes
© 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/).