1. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B*57 protection against HIV-1
- Author
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Xiaojiang Gao, Stephen A. Migueles, Steven G. Deeks, Bruce D. Walker, Florencia P Segal, Emma Gostick, Zabrina L. Brumme, Mary Carrington, James J. Goedert, Nelson L. Michael, Jonathan M. Carlson, Ying Qi, Patrick R. Shea, David Price, Steven M. Wolinsky, Vivek Naranbhai, Julian P. Vivian, Nicolas Vince, Rasmi Thomas, Sian Llewellyn-Lacey, Maureen P. Martin, Jacques Fellay, Bernard A. P. Lafont, Veron Ramsuran, Jamie Rossjohn, David W. Haas, Shu Cheng Wong, Andrew G. Brooks, Philippa M. Saunders, Mark Connors, Jacqueline M.L. Widjaja, Phillip Pymm, Cancer and Inflammation Program [Frederick, MD, USA] (Leidos Biomedical Research Inc.), Frederick National Laboratory for Cancer Research (FNLCR)-NCI-Frederick, Ragon Institute of MGH, MIT and Harvard, Centre for the AIDS Programme of Research [Durban, South Africa] (CAPRISA), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN), Institute for Genomic Medicine [New York, NY, USA], Columbia University [New York], KwaZulu-Natal Research Innovation and Sequencing Platform [Durban, South Africa] (KRISP), University of KwaZulu-Natal [Durban, Afrique du Sud] (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Translational ImmunoGenetic in AutoImmunity and Transplantation (Team 5 - U1064 Inserm - CRTI), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), US Military HIV Research Program [Silver Spring, MD, USA], Walter Reed Army Institute of Research, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), Faculty of Health Sciences [Burnaby, BC, Canada], Simon Fraser University (SFU.ca), British Columbia Centre for Excellence in HIV/AIDS [Vancouver, BC, Canada], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Division of Infectious Diseases [Chicago, IL, USA], Northwestern University Feinberg School of Medicine, Infections and Immunoepidemiology Branch [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), San Francisco General Hospital Medical Center [San Francisco, CA, USA], Vanderbilt University School of Medicine [Nashville], Laboratory of Immunoregulation [Bethesda, MD, USA], National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), School of Life Sciences [Lausanne], Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff], Non-Human Primate Immunogenetics and Cellular Immunology Unit [Bethesda, MD, USA], National Institutes of Health [Bethesda] (NIH)-National Institute of Allergy and Infectious Deseases (NIAID), Human Immunology Section [Bethesda, MD, USA] (Vaccine Research Center), Viral Immunology Section [Bethesda, MD, USA] (Office of the Scientific Director), Infection and Immunity Program [Victoria, Australia] (Department of Biochemistry and Molecular Biology), Monash University [Clayton]-Biomedicine Discovery Institute [Victoria, Australia]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia], Department of Microbiology and Immunology [Victoria, Australia], University of Melbourne-Peter Doherty Institute for Infection and Immunity [Victoria, Australia], This work was supported by federal funds from the NCI, NIH, under contract HHSN261200800001E., Le Bihan, Sylvie, University of KwaZulu-Natal (UKZN), University of KwaZulu-Natal (UKZN)-School of Laboratory Medicine and Medical Sciences [Durban, South Africa], Institute of Medical Genetics [Cardiff]-Cardiff University, and Monash University [Clayton]-Australian Research Council Centre of Excellence in Advanced Molecular Imaging [Victoria, Australia]-Biomedicine Discovery Institute [Victoria, Australia]
- Subjects
0301 basic medicine ,Adult ,Male ,T cell ,Killer-cell immunoglobulin-like receptor ,Immunology ,HIV Infections ,NK cells ,Medical and Health Sciences ,AIDS/HIV ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,KIR3DL1 ,Clinical Research ,MHC class I ,Receptors ,medicine ,HLA-B Antigens ,2.1 Biological and endogenous factors ,Humans ,Aetiology ,Receptor ,MHC class 1 ,Innate immunity ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,biology ,Genetic Variation ,Receptors, KIR3DL1 ,General Medicine ,Middle Aged ,Molecular biology ,Allotype ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Good Health and Well Being ,biology.protein ,HIV-1 ,HIV/AIDS ,Female ,Infection ,CD8 ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030215 immunology ,Research Article - Abstract
International audience; HLA-B*57 control of HIV involves enhanced CD8+ T cell responses against infected cells, but extensive heterogeneity exists in the level of HIV control among B*57+ individuals. Using whole-genome sequencing of untreated B*57+ HIV-1-infected controllers and noncontrollers, we identified a single variant (rs643347A/G) encoding an isoleucine-to-valine substitution at position 47 (I47V) of the inhibitory killer cell immunoglobulin-like receptor KIR3DL1 as the only significant modifier of B*57 protection. The association was replicated in an independent cohort and across multiple outcomes. The modifying effect of I47V was confined to B*57:01 and was not observed for the closely related B*57:03. Positions 2, 47, and 54 tracked one another nearly perfectly, and 2 KIR3DL1 allotypes differing only at these 3 positions showed significant differences in binding B*57:01 tetramers, whereas the protective allotype showed lower binding. Thus, variation in an immune NK cell receptor that binds B*57:01 modifies its protection. These data highlight the exquisite specificity of KIR-HLA interactions in human health and disease.
- Published
- 2017