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

Paul J Norman; Laurent Abi-Rached; Ketevan Gendzekhadze; Daniel Korbel; Michael Gleimer; Don Rowley; Dan Bruno; Christine V F Carrington; Dasdayanee Chandanayingyong; Yih-Hsin Chang; Catalina Crespí; Güher Saruhan-Direskeneli; Patricia A Fraser; Kamran Hameed; Giorgi Kamkamidze; Kwadwo A Koram; Zulay Layrisse; Nuria Matamoros; Joan Milà; Myoung Hee Park; Ramasamy M Pitchappan; D Dan Ramdath; Ming-Yuh Shiau; Henry A F Stephens; Siske Struik; David H Verity; Robert W Vaughan; Dolly Tyan; Ronald W Davis; Eleanor M Riley; Mostafa Ronaghi; Peter Parham

doi:10.1038/ng2111

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

Paul J Norman, Laurent Abi-Rached, Ketevan Gendzekhadze, Daniel Korbel, Michael Gleimer, Don Rowley, Dan Bruno, Christine V F Carrington, Dasdayanee Chandanayingyong, Yih-Hsin Chang, Catalina Crespí, Güher Saruhan-Direskeneli, Patricia A Fraser, Kamran Hameed, Giorgi Kamkamidze, Kwadwo A Koram, Zulay Layrisse, Nuria Matamoros, Joan Milà, Myoung Hee ParkRamasamy M Pitchappan, D Dan Ramdath, Ming-Yuh Shiau, Henry A F Stephens, Siske Struik, David H Verity, Robert W Vaughan, Dolly Tyan, Ronald W Davis, Eleanor M Riley, Mostafa Ronaghi, Peter Parham

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1092-9
Number of pages	8
Journal	Nature Genetics
Volume	39
Issue number	9
DOIs	https://doi.org/10.1038/ng2111
Publication status	Published - Sep 2007

Keywords

African Continental Ancestry Group/genetics
Alleles
Amino Acid Sequence
Binding Sites/genetics
Gene Frequency
Genetics, Population
HLA-B Antigens/chemistry
Humans
Linkage Disequilibrium
Molecular Sequence Data
Phylogeny
Polymorphism, Genetic
Protein Structure, Tertiary
Receptors, KIR3DL1/chemistry
Receptors, KIR3DS1/chemistry
Selection, Genetic
Sequence Homology, Amino Acid

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Norman, P. J., Abi-Rached, L., Gendzekhadze, K., Korbel, D., Gleimer, M., Rowley, D., Bruno, D., Carrington, C. V. F., Chandanayingyong, D., Chang, Y-H., Crespí, C., Saruhan-Direskeneli, G., Fraser, P. A., Hameed, K., Kamkamidze, G., Koram, K. A., Layrisse, Z., Matamoros, N., Milà, J., ... Parham, P. (2007). Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans. Nature Genetics, 39(9), 1092-9. https://doi.org/10.1038/ng2111

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title = "Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans",

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.",

keywords = "African Continental Ancestry Group/genetics, Alleles, Amino Acid Sequence, Binding Sites/genetics, Gene Frequency, Genetics, Population, HLA-B Antigens/chemistry, Humans, Linkage Disequilibrium, Molecular Sequence Data, Phylogeny, Polymorphism, Genetic, Protein Structure, Tertiary, Receptors, KIR3DL1/chemistry, Receptors, KIR3DS1/chemistry, Selection, Genetic, Sequence Homology, Amino Acid",

author = "Norman, {Paul J} and Laurent Abi-Rached and Ketevan Gendzekhadze and Daniel Korbel and Michael Gleimer and Don Rowley and Dan Bruno and Carrington, {Christine V F} and Dasdayanee Chandanayingyong and Yih-Hsin Chang and Catalina Cresp{\'i} and G{\"u}her Saruhan-Direskeneli and Fraser, {Patricia A} and Kamran Hameed and Giorgi Kamkamidze and Koram, {Kwadwo A} and Zulay Layrisse and Nuria Matamoros and Joan Mil{\`a} and Park, {Myoung Hee} and Pitchappan, {Ramasamy M} and Ramdath, {D Dan} and Ming-Yuh Shiau and Stephens, {Henry A F} and Siske Struik and Verity, {David H} and Vaughan, {Robert W} and Dolly Tyan and Davis, {Ronald W} and Riley, {Eleanor M} and Mostafa Ronaghi and Peter Parham",

year = "2007",

month = sep,

doi = "10.1038/ng2111",

language = "English",

volume = "39",

pages = "1092--9",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "9",

}

Norman, PJ, Abi-Rached, L, Gendzekhadze, K, Korbel, D, Gleimer, M, Rowley, D, Bruno, D, Carrington, CVF, Chandanayingyong, D, Chang, Y-H, 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, M-Y, Stephens, HAF, Struik, S, Verity, DH, Vaughan, RW, Tyan, D, Davis, RW, Riley, EM, Ronaghi, M & Parham, P 2007, 'Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans', Nature Genetics, vol. 39, no. 9, pp. 1092-9. https://doi.org/10.1038/ng2111

TY - JOUR

T1 - Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans

AU - Norman, Paul J

AU - Abi-Rached, Laurent

AU - Gendzekhadze, Ketevan

AU - Korbel, Daniel

AU - Gleimer, Michael

AU - Rowley, Don

AU - Bruno, Dan

AU - Carrington, Christine V F

AU - Chandanayingyong, Dasdayanee

AU - Chang, Yih-Hsin

AU - Crespí, Catalina

AU - Saruhan-Direskeneli, Güher

AU - Fraser, Patricia A

AU - Hameed, Kamran

AU - Kamkamidze, Giorgi

AU - Koram, Kwadwo A

AU - Layrisse, Zulay

AU - Matamoros, Nuria

AU - Milà, Joan

AU - Park, Myoung Hee

AU - Pitchappan, Ramasamy M

AU - Ramdath, D Dan

AU - Shiau, Ming-Yuh

AU - Stephens, Henry A F

AU - Struik, Siske

AU - Verity, David H

AU - Vaughan, Robert W

AU - Tyan, Dolly

AU - Davis, Ronald W

AU - Riley, Eleanor M

AU - Ronaghi, Mostafa

AU - Parham, Peter

PY - 2007/9

Y1 - 2007/9

N2 - 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.

AB - 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.

KW - African Continental Ancestry Group/genetics

KW - Alleles

KW - Amino Acid Sequence

KW - Binding Sites/genetics

KW - Gene Frequency

KW - Genetics, Population

KW - HLA-B Antigens/chemistry

KW - Humans

KW - Linkage Disequilibrium

KW - Molecular Sequence Data

KW - Phylogeny

KW - Polymorphism, Genetic

KW - Protein Structure, Tertiary

KW - Receptors, KIR3DL1/chemistry

KW - Receptors, KIR3DS1/chemistry

KW - Selection, Genetic

KW - Sequence Homology, Amino Acid

U2 - 10.1038/ng2111

DO - 10.1038/ng2111

M3 - Article

C2 - 17694054

VL - 39

SP - 1092

EP - 1099

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 9

ER -

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

Abstract

Keywords

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