NKG2C sequence polymorphism modulates the expansion of adaptive NK cells in response to human CMV

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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 2025-01-08T07:26:57Z
• dc.date.available 2025-01-08T07:26:57Z
• dc.date.issued 2024
• dc.description.abstract A subpopulation of NK cells with distinctive phenotype and function differentiates and expands specifically in response to infection by human cytomegalovirus (HCMV). A hallmark of these adaptive NK cells is their increased expression levels of the activating CD94/NKG2C receptor for HLA-E, and lack of expression of its inhibitory homologue CD94/NKG2A. Their frequency is highly variable in HCMV+ individuals, and the basis for such differences is only partially understood. Here, we explore the possible influence of sequence polymorphism of the NKG2C (or KLRC2) gene on the expansion of NKG2C+NKG2A- NK cells in healthy HCMV-seropositive donors. Our results show a significant association of greater proportions of adaptive NK cells with allele NKG2C*02. This is defined by two amino acid substitutions in comparison with the most prevalent allele, NKG2C*01, and associates with additional sequence polymorphisms in noncoding regions. Furthermore, we demonstrate consistently higher mRNA levels of NKG2C*02 in heterozygous individuals co-expressing this allele in combination with NKG2C*01 or *03. This predominance is independent of polymorphisms in the promoter and 3' UTRs and is appreciated also in HCMV-seronegative donors. In summary, although additional factors are most likely implicated in the variable expansion of NKG2C+NKG2A- NK cells in response to HCMV, our results demonstrate that host immunogenetics, in particular NKG2C diversity, influences the magnitude of such response.
• dc.description.sponsorship This work supported by grant EU FP7-MINECO Infect-ERA program (PCIN-2015-191-C02-01/02), AEI/FEDER, EU (PID2019-110609RB-C22/AEI/10.13039/501100011033). Manuela Moraru and Judit Asenjo 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Asenjo J, Moraru M, Al-Akioui-Sanz K, Altadill M, Muntasell A, López-Botet M, et al. NKG2C sequence polymorphism modulates the expansion of adaptive NK cells in response to human CMV. HLA. 2024 Nov;104(5):e15764. DOI: 10.1111/tan.15764
• dc.identifier.doi http://dx.doi.org/10.1111/tan.15764
• dc.identifier.issn 2059-2302
• dc.identifier.uri http://hdl.handle.net/10230/68999
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof HLA. 2024 Nov;104(5):e15764
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22
• dc.rights © 2024 The Author(s). 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 (http://creativecommons.org/licenses/by-nc-nd/4.0/), 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 NKG2C receptor
• dc.subject.keyword Alleles
• dc.subject.keyword Cytomegalovirus
• dc.subject.keyword Genetic polymorphism
• dc.subject.keyword Human genetics
• dc.subject.keyword Natural killer cell lectin‐like receptors
• dc.title NKG2C sequence polymorphism modulates the expansion of adaptive NK cells in response to human CMV
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion