Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.
Norman PJ,
Abi-Rached L,
Gendzekhadze K,
Korbel D,
Gleimer M,
Rowley D,
Bruno D,
Carrington CV,
Chandanayingyong D,
Chang YH,
Crespí C,
Saruhan-Direskeneli G,
Fraser PA,
Hameed K,
Kamkamidze G,
Koram KA,
Layrisse Z,
Matamoros N,
Milà J,
Park MH,
Pitchappan RM,
Ramdath DD,
Shiau MY,
Stephens HA,
Struik S,
Verity DH,
Vaughan RW,
Tyan D,
Davis RW,
Riley EM,
Ronaghi M,
Parham P.
Department of Structural Biology, Stanford University School of Medicine, Stanford, California 94305, USA. paul.norman@stanford.edu
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.
PMID: 17694054 [PubMed - indexed for MEDLINE]