Asenjo, JuditMoraru, ManuelaAl-Akioui-Sanz, KarimaAltadill, MireiaMuntasell i Castellví, Aura, 1972-López-Botet, M. (Miguel)Vilches, Carlos2025-01-082025-01-082024Asenjo 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.157642059-2302http://hdl.handle.net/10230/68999A 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.application/pdfeng© 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.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1111/tan.15764NKG2C receptorAllelesCytomegalovirusGenetic polymorphismHuman geneticsNatural killer cell lectin‐like receptorsinfo:eu-repo/semantics/openAccess