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KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans

INTRODUCTION: KIR2DS5 is an activating human NK cell receptor of lineage III KIR. These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that recognize either the C1 or C2 epitope of HLA‐C. In Europeans KIR2DS5 is essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering...

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Autores principales: Blokhuis, Jeroen H., Hilton, Hugo G., Guethlein, Lisbeth A., Norman, Paul J., Nemat‐Gorgani, Neda, Nakimuli, Annettee, Chazara, Olympe, Moffett, Ashley, Parham, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691316/
https://www.ncbi.nlm.nih.gov/pubmed/28685972
http://dx.doi.org/10.1002/iid3.178
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author Blokhuis, Jeroen H.
Hilton, Hugo G.
Guethlein, Lisbeth A.
Norman, Paul J.
Nemat‐Gorgani, Neda
Nakimuli, Annettee
Chazara, Olympe
Moffett, Ashley
Parham, Peter
author_facet Blokhuis, Jeroen H.
Hilton, Hugo G.
Guethlein, Lisbeth A.
Norman, Paul J.
Nemat‐Gorgani, Neda
Nakimuli, Annettee
Chazara, Olympe
Moffett, Ashley
Parham, Peter
author_sort Blokhuis, Jeroen H.
collection PubMed
description INTRODUCTION: KIR2DS5 is an activating human NK cell receptor of lineage III KIR. These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that recognize either the C1 or C2 epitope of HLA‐C. In Europeans KIR2DS5 is essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering investigations showed that KIR2DS5*002 has activating potential, but cannot recognize HLA‐A, ‐B, or ‐C. Subsequent studies have shown that KIR2DS5 is highly polymorphic in Africans, and that KIR2DS5*006 protects pregnant Ugandan women from preeclampsia. Because inhibitory C2‐specific KIR2DL1 correlates with preeclampsia, whereas activating C2‐specific KIR2DS1 protects, this association pointed to KIR2DS5*006 being an activating C2‐specific receptor. To test this hypothesis we made KIR‐Fc fusion proteins from all ten KIR2DS5 allotypes and tested their binding to a representative set of HLA‐A, ‐B and ‐C allotypes. RESULTS: Six African‐specific KIR2DS5 bound to C2(+)HLA‐C but not to other HLA class I. Their avidity for C2 is ∼20% that of C2‐specific KIR2DL1 and ∼40% that of C2‐specific KIR2DS1. Among the African C2 receptors is KIR2DS5*006, which protected a cohort of pregnant Ugandans from pre‐eclampsia. Three African KIR2DS5 allotypes and KIR2DS5*002, bound no HLA‐A, ‐B or ‐C. As a group the C2‐binding KIR2DS5 allotypes protect against pre‐eclampsia compared to the non‐binding KIR2DS5 allotypes. Natural substitutions that contribute to loss or reduction of C2 receptor function are at positions 127, 158, and 176 in the D2 domain. CONCLUSIONS: KIR2DS5*005 has the KIR2DS5 consensus sequence, is the only allele found at both centromeric and telomeric locations of KIR2DS5, and is likely the common ancestor of all KIR2DS5 alleles. That KIR2DS5*005 has C2 receptor activity, points to KIR2DS5*002, and other allotypes lacking C2 receptor function, being products of attenuation, a characteristic feature of most KIR B haplotype genes. Alleles encoding attenuated and active KIR2DS5 are present in both centromeric and telomeric locations.
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spelling pubmed-56913162017-11-24 KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans Blokhuis, Jeroen H. Hilton, Hugo G. Guethlein, Lisbeth A. Norman, Paul J. Nemat‐Gorgani, Neda Nakimuli, Annettee Chazara, Olympe Moffett, Ashley Parham, Peter Immun Inflamm Dis Original Research INTRODUCTION: KIR2DS5 is an activating human NK cell receptor of lineage III KIR. These include both inhibitory KIR2DL1, 2 and 3 and activating KIR2DS1 that recognize either the C1 or C2 epitope of HLA‐C. In Europeans KIR2DS5 is essentially monomorphic, with KIR2DS5*002 being predominant. Pioneering investigations showed that KIR2DS5*002 has activating potential, but cannot recognize HLA‐A, ‐B, or ‐C. Subsequent studies have shown that KIR2DS5 is highly polymorphic in Africans, and that KIR2DS5*006 protects pregnant Ugandan women from preeclampsia. Because inhibitory C2‐specific KIR2DL1 correlates with preeclampsia, whereas activating C2‐specific KIR2DS1 protects, this association pointed to KIR2DS5*006 being an activating C2‐specific receptor. To test this hypothesis we made KIR‐Fc fusion proteins from all ten KIR2DS5 allotypes and tested their binding to a representative set of HLA‐A, ‐B and ‐C allotypes. RESULTS: Six African‐specific KIR2DS5 bound to C2(+)HLA‐C but not to other HLA class I. Their avidity for C2 is ∼20% that of C2‐specific KIR2DL1 and ∼40% that of C2‐specific KIR2DS1. Among the African C2 receptors is KIR2DS5*006, which protected a cohort of pregnant Ugandans from pre‐eclampsia. Three African KIR2DS5 allotypes and KIR2DS5*002, bound no HLA‐A, ‐B or ‐C. As a group the C2‐binding KIR2DS5 allotypes protect against pre‐eclampsia compared to the non‐binding KIR2DS5 allotypes. Natural substitutions that contribute to loss or reduction of C2 receptor function are at positions 127, 158, and 176 in the D2 domain. CONCLUSIONS: KIR2DS5*005 has the KIR2DS5 consensus sequence, is the only allele found at both centromeric and telomeric locations of KIR2DS5, and is likely the common ancestor of all KIR2DS5 alleles. That KIR2DS5*005 has C2 receptor activity, points to KIR2DS5*002, and other allotypes lacking C2 receptor function, being products of attenuation, a characteristic feature of most KIR B haplotype genes. Alleles encoding attenuated and active KIR2DS5 are present in both centromeric and telomeric locations. John Wiley and Sons Inc. 2017-07-06 /pmc/articles/PMC5691316/ /pubmed/28685972 http://dx.doi.org/10.1002/iid3.178 Text en © 2017 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Blokhuis, Jeroen H.
Hilton, Hugo G.
Guethlein, Lisbeth A.
Norman, Paul J.
Nemat‐Gorgani, Neda
Nakimuli, Annettee
Chazara, Olympe
Moffett, Ashley
Parham, Peter
KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title_full KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title_fullStr KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title_full_unstemmed KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title_short KIR2DS5 allotypes that recognize the C2 epitope of HLA‐C are common among Africans and absent from Europeans
title_sort kir2ds5 allotypes that recognize the c2 epitope of hla‐c are common among africans and absent from europeans
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691316/
https://www.ncbi.nlm.nih.gov/pubmed/28685972
http://dx.doi.org/10.1002/iid3.178
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