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Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans

Cited 167 time in Web of Science Cited 171 time in Scopus
Authors
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
2007
Publisher
Nature Publishing Group
Citation
Nat. Genet. 39, 1092-1099
Keywords
African Continental Ancestry Group/*geneticsAllelesAmino Acid SequenceBinding Sites/geneticsGene FrequencyGenetics, PopulationHLA-B Antigens/chemistry/geneticsLinkage DisequilibriumMolecular Sequence DataPhylogenyPolymorphism, GeneticProtein Structure, TertiaryReceptors, KIR3DL1/chemistry/*geneticsReceptors, KIR3DS1/chemistry/*genetics*Selection (Genetics)Sequence Homology, Amino Acid
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.
ISSN
1061-4036 (Print)
Language
English
URI
http://www.nature.com/ng/journal/v39/n9/abs/ng2111.html

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17694054

http://hdl.handle.net/10371/12122
DOI
https://doi.org/10.1038/ng2111
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College of Medicine/School of Medicine (의과대학/대학원)Laboratory Medicine (검사의학전공)Journal Papers (저널논문_검사의학전공)
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