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

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• dc.contributor.author Asenjo, Judit
• dc.contributor.author Moraru, Manuela
• dc.contributor.author Al-Akioui-Sanz, Karima
• dc.contributor.author Altadill, Mireia
• dc.contributor.author Muntasell i Castellví, Aura, 1972-
• dc.contributor.author López-Botet, M. (Miguel)
• dc.contributor.author Vilches, Carlos
• dc.date.accessioned 2022-09-07T06:22:08Z
• dc.date.available 2022-09-07T06:22:08Z
• dc.date.issued 2022
• dc.description.abstract 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.
• dc.description.sponsorship 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).
• dc.format.mimetype application/pdf
• dc.identifier.citation Asenjo J, Moraru M, Al-Akioui-Sanz K, Altadill M, Muntasell A, López-Botet M, Vilches C. Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions. HLA. 2022 Nov;100(5):469-78. DOI: 10.1111/tan.14734
• dc.identifier.doi http://dx.doi.org/10.1111/tan.14734
• dc.identifier.issn 2059-2302
• dc.identifier.uri http://hdl.handle.net/10230/54008
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof HLA. 2022 Nov;100(5):469-78
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2016-80363-C2-2-R
• dc.rights © 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.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword HLA-E
• dc.subject.keyword NKG2C receptor
• dc.subject.keyword Alleles
• dc.subject.keyword Genetic polymorphism
• dc.subject.keyword Human genetics
• dc.subject.keyword Natural killer cell lectin-like receptors
• dc.title Diversity of NKG2C genotypes in a European population: Conserved and recombinant haplotypes in the coding, promoter, and 3'-untranslated regions
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion