guest ::
| Home > Articles > Published articles > Sequence Polymorphism Modulates the Expansion of Adaptive Cells in Response to Human |
| Home > Articles > Published articles > Sequence Polymorphism Modulates the Expansion of Adaptive Cells in Response to Human |
(Instituto de Investigación Sanitaria Puerta de Hierro) (Universitat Pompeu Fabra) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia) (Institut Hospital del Mar d'Investigacions Mèdiques) (Ministerio de Sanidad)
| Date: | 2024 |
| 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. |
| Grants: | Ministerio de Economía y Competitividad PCIN-2015-191-C02-01 Ministerio de Economía y Competitividad PCIN-2015-191-C02-002 Agencia Estatal de Investigación PID2019-110609RB-C22 Agencia Estatal de Investigación SAF2016-80363-C2-2-R |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Alleles ; Cytomegalovirus ; Genetic polymorphism ; Human genetics ; Natural killer cell lectin-like receptors ; NKG2C receptor |
| Published in: | Hla, Vol. 104, Issue 5 (November 2024) , art. e15764, ISSN 2059-2310 |
