title: Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.
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.
authors: Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA. paul.norman@stanford.edu
authors: Paul J
authors: PJ
authors: Norman
authors: Laurent
authors: L
authors: Abi-Rached
authors: Ketevan
authors: K
authors: Gendzekhadze
authors: Daniel
authors: D
authors: Korbel
authors: Michael
authors: M
authors: Gleimer
authors: Don
authors: D
authors: Rowley
authors: Dan
authors: D
authors: Bruno
authors: Christine V F
authors: CV
authors: Carrington
authors: Dasdayanee
authors: D
authors: Chandanayingyong
authors: Yih-Hsin
authors: YH
authors: Chang
authors: Catalina
authors: C
authors: Crespí
authors: Güher
authors: G
authors: Saruhan-Direskeneli
authors: Patricia A
authors: PA
authors: Fraser
authors: Kamran
authors: K
authors: Hameed
authors: Giorgi
authors: G
authors: Kamkamidze
authors: Kwadwo A
authors: KA
authors: Koram
authors: Zulay
authors: Z
authors: Layrisse
authors: Nuria
authors: N
authors: Matamoros
authors: Joan
authors: J
authors: Milà
authors: Myoung Hee
authors: MH
authors: Park
authors: Ramasamy M
authors: RM
authors: Pitchappan
authors: D Dan
authors: DD
authors: Ramdath
authors: Ming-Yuh
authors: MY
authors: Shiau
authors: Henry A F
authors: HA
authors: Stephens
authors: Siske
authors: S
authors: Struik
authors: David H
authors: DH
authors: Verity
authors: Robert W
authors: RW
authors: Vaughan
authors: Dolly
authors: D
authors: Tyan
authors: Ronald W
authors: RW
authors: Davis
authors: Eleanor M
authors: EM
authors: Riley
authors: Mostafa
authors: M
authors: Ronaghi
authors: Peter
authors: P
authors: Parham
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D005828:Genetics, Population; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D054341:Receptors, KIR3DL1 / Q000737:chemistry / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000737:chemistry / Q000235:genetics*; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1