S-Space College of Medicine/School of Medicine (의과대학/대학원) Laboratory Medicine (검사의학전공) Journal Papers (저널논문_검사의학전공)
Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans
- Norman, Paul J; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Korbel, Daniel; Gleimer, Michael; Rowley, Don; Bruno, Dan; Carrington, Christine V F; Chandanayingyong, Dasdayanee; Chang, Yih-Hsin; Crespi, Catalina; Saruhan-Direskeneli, Guher; Fraser, Patricia A; Hameed, Kamran; Kamkamidze, Giorgi; Koram, Kwadwo A; Layrisse, Zulay; Matamoros, Nuria; Mila, Joan; Park, Myoung Hee; Pitchappan, Ramasamy M; Ramdath, D Dan; Shiau, Ming-Yuh; Stephens, Henry A F; Struik, Siske; Verity, David H; Vaughan, Robert W; Tyan, Dolly; Davis, Ronald W; Riley, Eleanor M; Ronaghi, Mostafa; Parham, Peter
- Issue Date
- Nature Publishing Group
- Nat. Genet. 39, 1092-1099
- African Continental Ancestry Group/*genetics; Alleles; Amino Acid Sequence; Binding Sites/genetics; Gene Frequency; Genetics, Population; HLA-B Antigens/chemistry/genetics; Linkage Disequilibrium; Molecular Sequence Data; Phylogeny; Polymorphism, Genetic; Protein Structure, Tertiary; Receptors, KIR3DL1/chemistry/*genetics; Receptors, KIR3DS1/chemistry/*genetics; *Selection (Genetics); Sequence Homology, Amino Acid
- 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.
- 1061-4036 (Print)
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