Sequence Polymorphism Modulates the Expansion of Adaptive Cells in Response to Human
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 o...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:319935 |
| Acceso en línea: | https://ddd.uab.cat/record/319935 https://dx.doi.org/urn:doi:10.1111/tan.15764 |
| Access Level: | acceso abierto |
| Palabra clave: | Alleles Cytomegalovirus Genetic polymorphism Human genetics Natural killer cell lectin-like receptors NKG2C receptor |
| Sumario: | 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. |
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