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

P J Norman, L bi-Rached, K Gendzekhadze, D Korbel, M Gleimer, D Rowley, D Bruno, C V F Carrington, D Chandanayingyong, Y H Chang, C Crespi, G Saruhan-Direskeneli, P A Fraser, K Hameed, G Kamkamidze, K A Koram, Z Layrisse, N Matamoros, J Mila, M H ParkR M Pitchappan, D D Ramdath, M Y Shiau, H A F Stephens, S Struik, D H Verity, D Tyan, R W Davis, E M Riley, M Ronaghi, P Parham, Robert Vaughan

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194 Citations (Scopus)


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 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
Original languageEnglish
Pages (from-to)1092 - 1099
Number of pages8
JournalNature Genetics
Issue number9
Publication statusPublished - Sept 2007


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