2026-04-14T08:46:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/689992025-12-26T11:25:59Zcom_2072_6col_2072_452952

NKG2C sequence polymorphism modulates the expansion of adaptive NK cells in response to human CMV Asenjo, Judit Moraru, Manuela Al-Akioui-Sanz, Karima Altadill, Mireia Muntasell i Castellví, Aura, 1972- López-Botet, M. (Miguel) Vilches, Carlos NKG2C receptor Alleles Cytomegalovirus Genetic polymorphism Human genetics Natural killer cell lectin‐like receptors 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. 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. 2025-01-08T07:26:57Z 2025-01-08T07:26:57Z 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion HLA. 2024 Nov;104(5):e15764 info:eu-repo/grantAgreement/ES/2PE/PID2019-110609RB-C22 © 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. http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Wiley