An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania

Artículo

 

Te invitamos a leer el artículo "An archaic HLA class I receptor allele diversifies natural killer cell-driven immunity in First Nations peoples of Oceania" publicado en Cell, a cargo del profesor investigador Dr. Andrés Moreno y su equipo de trabajo de la UGA.

Autores: Liyen Loh / Philippa M. Saunders / Camilla Faoro / Neus Font-Porterias / Neda Nemat-Gorgani / Genelle F. Harrison / Suraju Sadeeq / Luca Hensen / Shu Cheng Wong / Jacqueline Widjaja / E. Bridie Clemens / Shiying Zhu / Katherine M. Kichula / Sudan Tao / Faming Zhu / Gonzalo Montero-Martin / Marcelo Fernandez-Vina / Lisbeth A. Guethlein / Julian P. Vivian / Jane Davies / Alexander J. Mentzer / Stephen J. Oppenheimer / William Pomat / Alexander G. Ioannidis / Carmina Barberena-Jonas / Oceanian Genome Variation Project Consortium / Andrés Moreno-Estrada / Adrian Miller / Peter Parham / Jamie Rossjohn / Steven Y.C. Tong / Katherine Kedzierska / Andrew G. Brooks / Paul J. Norman

  1. Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia

  2. Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, USA

  3. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia

  4. Department of Biomedical Informatics, University of Colorado School of Medicine, Aurora, USA

  5. Department of Structural Biology and Department of Microbiology and Immunology, Stanford University, Stanford, USA

  6. Blood Center of Zhejiang Province, Hangzhou, Zhejiang, China

  7. Stanford Blood Centre, Department of Pathology, Stanford University, Stanford, USA

  8. Menzies School of Health Research, Charles Darwin University, Darwin, Australia

  9. Department of Infectious Diseases, Royal Darwin Hospital, Casuarina, Australia

  10. Wellcome Centre for Human Genetics, University of Oxford, UK

  11. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, UK

  12. Institute of Social and Cultural Anthropology, School of Anthropology and Museum Ethnography, University of Oxford, UK

  13. Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea

  14. Department of Biomolecular Engineering, UC Santa Cruz, Santa Cruz, USA

  15. Advanced Genomics Unit, Center for Research and Advanced Studies (Cinvestav), Mexico

  16. Jawun Research Centre, Central Queensland University, Cairns, Australia

  17. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, UK

  18. Victorian Infectious Diseases Service, The Royal Melbourne Hospital, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia

  19. Department of Infectious Diseases, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia

Felicitamos al estudiantado y profesorado que contribuyeron en esta investigación por su arduo trabajo.

Summary:

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-A24:02 became the dominant ligand for inhibitory KIR3DL1 in First Nations peoples across Oceania, through positive natural selection. We identify KIR3DL1114, widespread across and unique to Oceania, as an allele lineage derived from archaic humans. KIR3DL1114+NK cells from First Nations Australian donors are inhibited through binding HLA-A24:02. The KIR3DL1114 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.


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11/11/2024 01:41:23 p. m.