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 ; Sequence Homology, Amino Acid ; Selection (Genetics)
- 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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