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Title: Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans
Authors: Paul J. Norman
Laurent Abi-Rached
Ketevan Gendzekhadze
Daniel Korbel
Michael Gleimer
Don Rowley
Dan Bruno
Christine V.F. Carrington
Dasdayanee Chandanayingyong
Yih Hsin Chang
Catalina Crespí
Güher Saruhan-Direskeneli
Patricia A. Fraser
Kamran Hameed
Giorgi Kamkamidze
Kwadwo A. Koram
Zulay Layrisse
Nuria Matamoros
Joan Milà
Myoung Hee Park
Ramasamy M. Pitchappan
D. Dan Ramdath
Ming Yuh Shiau
Henry A.F. Stephens
Siske Struik
David H. Verity
Robert W. Vaughan
Dolly Tyan
Ronald W. Davis
Eleanor M. Riley
Mostafa Ronaghi
Peter Parham
Stanford University School of Medicine
London School of Hygiene & Tropical Medicine
University of The West Indies Trinidad and Tobago
Mahidol University
Chung Shan Medical University
Hospital Universitario Son Espases
Istanbul Tip Fakultesi
Immune Disease Institute, Inc. Boston
The Aga Khan University Hospital
Rea Rehabilitation Centre
University of Ghana
Instituto Venezolano de Investigaciones Cientificas
Seoul National University College of Medicine
Madurai Kamaraj University
Hung Kuang University Taiwan
UCL Medical School
Moorfields Eye Hospital NHS Foundation Trust
King's College London
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Sep-2007
Citation: Nature Genetics. Vol.39, No.9 (2007), 1092-1099
Abstract: Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression. © 2007 Nature Publishing Group.
ISSN: 15461718
Appears in Collections:Scopus 2006-2010

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