Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions

NK cells monitor altered molecular patterns in tumors and infected cells through an ample array of receptors. Two families of evolutionarily distant receptors have converged to enable human NK cells to sense levels of HLA class I ligands, frequently abnormal in altered cells. Whilst different forms...

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Autores: Asenjo, Judit, Moraru, Manuela, Al-Akioui-Sanz, Karima, Altadill, Mireia, Muntasell i Castellví, Aura, 1972-, López-Botet, M. (Miguel), Vilches, Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/54008
Acceso en línea:http://hdl.handle.net/10230/54008
http://dx.doi.org/10.1111/tan.14734
Access Level:acceso abierto
Palabra clave:HLA-E
NKG2C receptor
Alleles
Genetic polymorphism
Human genetics
Natural killer cell lectin-like receptors
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spelling Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regionsAsenjo, JuditMoraru, ManuelaAl-Akioui-Sanz, KarimaAltadill, MireiaMuntasell i Castellví, Aura, 1972-López-Botet, M. (Miguel)Vilches, CarlosHLA-ENKG2C receptorAllelesGenetic polymorphismHuman geneticsNatural killer cell lectin-like receptorsNK cells monitor altered molecular patterns in tumors and infected cells through an ample array of receptors. Two families of evolutionarily distant receptors have converged to enable human NK cells to sense levels of HLA class I ligands, frequently abnormal in altered cells. Whilst different forms of polymorphism are a hallmark of killer-cell immunoglobulin-like receptors and their classic HLA-A, B, and C ligands, genetic diversity of killer-cell lectin-like receptors for the non-classical HLA-E (CD94/NKG2 heterodimers) is less conspicuous and has attracted less attention. A common pattern of diversification in both receptor families is evolution of pairs of inhibitory and activating homologs for a common ligand, the genes encoding activating receptors being more frequently affected by copy number variation (CNV). This is exemplified by the gene encoding the activating NKG2C subunit (KLRC2 or NKG2C), which marks an NK-cell subpopulation that differentiates or expands in response to cytomegalovirus. We have studied NKG2C diversity in 240 South European individuals, using polymerase chain reaction and sequencing methods to assess both gene CNV and single-nucleotide polymorphisms (SNPs) affecting its promoter, coding and 3'-untranslated (3'UT) regions. Sequence analysis revealed eight common SNPs-one in the promoter, two in the coding sequence, and five in the 3'UT region. These SNPs associate strongly with each other, forming three conserved extended haplotypes (frequencies: 0.456, 0.221, and 0.117). Homo- and heterozygous combination of these, together with complete gene deletion (0.175) and additional haplotypes with frequencies lower than 0.015, generate a diversity of NKG2C genotypes of potential immunological importance.This article is dedicated to the memory of Benny P. Shum. We thank Dr. Elvira Ramil, from the DNA sequencing core facility of Instituto de Investigación Sanitaria Puerta de Hierro – Segovia de Arana, for continued support. This work was funded by grant PID2019-110609RB-C22/AEI/10.13039/501100011033 (AEI/FEDER, EU). MM and JA were hired by the latter grant and by GCB15152947MELE from the Asociación Española contra el Cáncer Foundation. Karima Al-Akioui-Sanz was supported sequentially by grant PEJ-2017-AI/BMD-7377, with co-financing by EU Youth Employment Initiative, European Social Fund (91.89%), and Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid; and by grant SAF2016-80363-C2-2-R (AEI/FEDER, EU).Wiley202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/54008http://dx.doi.org/10.1111/tan.14734reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésHLA. 2022 Nov;100(5):469-78info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-2-R© 2022 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/540082026-06-12T07:21:37Z
dc.title.none.fl_str_mv Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
title Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
spellingShingle Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
Asenjo, Judit
HLA-E
NKG2C receptor
Alleles
Genetic polymorphism
Human genetics
Natural killer cell lectin-like receptors
title_short Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
title_full Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
title_fullStr Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
title_full_unstemmed Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
title_sort Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
dc.creator.none.fl_str_mv Asenjo, Judit
Moraru, Manuela
Al-Akioui-Sanz, Karima
Altadill, Mireia
Muntasell i Castellví, Aura, 1972-
López-Botet, M. (Miguel)
Vilches, Carlos
author Asenjo, Judit
author_facet Asenjo, Judit
Moraru, Manuela
Al-Akioui-Sanz, Karima
Altadill, Mireia
Muntasell i Castellví, Aura, 1972-
López-Botet, M. (Miguel)
Vilches, Carlos
author_role author
author2 Moraru, Manuela
Al-Akioui-Sanz, Karima
Altadill, Mireia
Muntasell i Castellví, Aura, 1972-
López-Botet, M. (Miguel)
Vilches, Carlos
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv HLA-E
NKG2C receptor
Alleles
Genetic polymorphism
Human genetics
Natural killer cell lectin-like receptors
topic HLA-E
NKG2C receptor
Alleles
Genetic polymorphism
Human genetics
Natural killer cell lectin-like receptors
description NK cells monitor altered molecular patterns in tumors and infected cells through an ample array of receptors. Two families of evolutionarily distant receptors have converged to enable human NK cells to sense levels of HLA class I ligands, frequently abnormal in altered cells. Whilst different forms of polymorphism are a hallmark of killer-cell immunoglobulin-like receptors and their classic HLA-A, B, and C ligands, genetic diversity of killer-cell lectin-like receptors for the non-classical HLA-E (CD94/NKG2 heterodimers) is less conspicuous and has attracted less attention. A common pattern of diversification in both receptor families is evolution of pairs of inhibitory and activating homologs for a common ligand, the genes encoding activating receptors being more frequently affected by copy number variation (CNV). This is exemplified by the gene encoding the activating NKG2C subunit (KLRC2 or NKG2C), which marks an NK-cell subpopulation that differentiates or expands in response to cytomegalovirus. We have studied NKG2C diversity in 240 South European individuals, using polymerase chain reaction and sequencing methods to assess both gene CNV and single-nucleotide polymorphisms (SNPs) affecting its promoter, coding and 3'-untranslated (3'UT) regions. Sequence analysis revealed eight common SNPs-one in the promoter, two in the coding sequence, and five in the 3'UT region. These SNPs associate strongly with each other, forming three conserved extended haplotypes (frequencies: 0.456, 0.221, and 0.117). Homo- and heterozygous combination of these, together with complete gene deletion (0.175) and additional haplotypes with frequencies lower than 0.015, generate a diversity of NKG2C genotypes of potential immunological importance.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/54008
http://dx.doi.org/10.1111/tan.14734
url http://hdl.handle.net/10230/54008
http://dx.doi.org/10.1111/tan.14734
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv HLA. 2022 Nov;100(5):469-78
info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22
info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-2-R
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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