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 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

Internal Medicine, East Africa

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

200 Citations (Scopus)

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 (UK)
Pages (from-to)	1092-1099
Number of pages	8
Journal	Nature Genetics
Volume	39
Issue number	9
DOIs	https://doi.org/10.1038/ng2111
Publication status	Published - Sept 2007

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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), 1092-1099. https://doi.org/10.1038/ng2111

@article{1012327e46bb4b03a7a1ec0306674589,

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.",

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 Chang, \{Yih Hsin\} 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 Shiau, \{Ming Yuh\} 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",

note = "Funding Information: We thank all donors, phlebotomists and colleagues involved in sample preparation; D. Koechlein, M. Lawson and members of N. Pourmand{\textquoteright}s laboratory for technical advice; and M. Carrington, S. Cooper and D. Middleton{\textquoteright}s laboratories for further samples. M.G. is a Howard Hughes graduate scholar and D.K. a Boehringer Ingelheim Fonds graduate scholar. S.S. is a Wellcome Trust Training fellow, and P.J.N. is a Lymphoma Research Foundation fellow. This work was supported grants to P.P. from the US National Institutes of Health (AI17892, AI24258 and AI64520) and by the Leukaemia and Lymphoma Society of the USA.",

year = "2007",

month = sep,

doi = "10.1038/ng2111",

language = "English (UK)",

volume = "39",

pages = "1092--1099",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "9",

}

Norman, PJ, Abi-Rached, L, Gendzekhadze, K, Korbel, D, Gleimer, M, Rowley, D, Bruno, D, Carrington, CVF, 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, 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. 1092-1099. 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

N1 - Funding Information: We thank all donors, phlebotomists and colleagues involved in sample preparation; D. Koechlein, M. Lawson and members of N. Pourmand’s laboratory for technical advice; and M. Carrington, S. Cooper and D. Middleton’s laboratories for further samples. M.G. is a Howard Hughes graduate scholar and D.K. a Boehringer Ingelheim Fonds graduate scholar. S.S. is a Wellcome Trust Training fellow, and P.J.N. is a Lymphoma Research Foundation fellow. This work was supported grants to P.P. from the US National Institutes of Health (AI17892, AI24258 and AI64520) and by the Leukaemia and Lymphoma Society of the USA.

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.

UR - https://www.scopus.com/pages/publications/34548348144

U2 - 10.1038/ng2111

DO - 10.1038/ng2111

M3 - Article

C2 - 17694054

AN - SCOPUS:34548348144

SN - 1061-4036

VL - 39

SP - 1092

EP - 1099

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

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

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