2026-04-14T08:21:52Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Asenjo, Judit author Moraru, Manuela author Al-Akioui-Sanz, Karima author Altadill, Mireia author Muntasell i Castellví, Aura, 1972- author López-Botet, M. (Miguel) author Vilches, Carlos author 2025-01-08T07:26:57Z 2025-01-08T07:26:57Z 2024 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. NKG2C receptor Alleles Cytomegalovirus Genetic polymorphism Human genetics Natural killer cell lectin‐like receptors NKG2C sequence polymorphism modulates the expansion of adaptive NK cells in response to human CMV