1. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.
- Author
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Norman, Paul J., Abi-Rached, Laurent, Gendzekhadze, Ketevan, Korbel, Daniel, Gleimer, Michael, Rowley, Don, Bruno, Dan, Carrington, Christine V. F., Chandanayingyong, Dasdayanee, Yih-Hsin Chang, Crespí, Catalina, Saruhan-Direskeneli, Güher, Fraser, Patricia A., Hameed, Kamran, Kamkamidze, Giorgi, Koram, Kwadwo A, Layrisse, Zulay, Matamoros, Nuria, Milà, Joan, and Park, Myoung Hee
- Subjects
KILLER cells ,CELL receptors ,IMMUNOGLOBULIN genes ,HLA histocompatibility antigens ,AFRICANS ,EPITOPES - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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