Paul J. NormanLaurent Abi-RachedKetevan GendzekhadzeDaniel KorbelMichael GleimerDon RowleyDan BrunoChristine V.F. CarringtonDasdayanee ChandanayingyongYih Hsin ChangCatalina CrespíGüher Saruhan-DireskeneliPatricia A. FraserKamran HameedGiorgi KamkamidzeKwadwo A. KoramZulay LayrisseNuria MatamorosJoan MilàMyoung Hee ParkRamasamy M. PitchappanD. Dan RamdathMing Yuh ShiauHenry A.F. StephensSiske StruikDavid H. VerityRobert W. VaughanDolly TyanRonald W. DavisEleanor M. RileyMostafa RonaghiPeter ParhamStanford University School of MedicineLondon School of Hygiene & Tropical MedicineUniversity of The West Indies Trinidad and TobagoMahidol UniversityChung Shan Medical UniversityHospital Universitario Son EspasesIstanbul Tip FakultesiImmune Disease Institute, Inc. BostonThe Aga Khan University HospitalRea Rehabilitation CentreUniversity of GhanaInstituto Venezolano de Investigaciones CientificasSeoul National University College of MedicineMadurai Kamaraj UniversityHung Kuang University TaiwanUCL Medical SchoolMoorfields Eye Hospital NHS Foundation TrustKing's College London2018-08-242018-08-242007-09-01Nature Genetics. Vol.39, No.9 (2007), 1092-109915461718106140362-s2.0-34548348144https://repository.li.mahidol.ac.th/handle/20.500.14594/24138Interactions 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/ng2111