Sequence Polymorphism Modulates the Expansion of Adaptive Cells in Response to Human
Asenjo, Judit (Instituto de Investigación Sanitaria Puerta de Hierro)
Moraru, Manuela (Instituto de Investigación Sanitaria Puerta de Hierro)
Al-Akioui-Sanz, Karima (Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana)
Altadill, Mireia (Universitat Pompeu Fabra)
Muntasell i Castellví, Aura 1972- (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
López-Botet, Miguel (Institut Hospital del Mar d'Investigacions Mèdiques)
Vilches, Carlos (Ministerio de Sanidad)

Fecha:	2024
Resumen:	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.
Ayudas:	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
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alleles ; Cytomegalovirus ; Genetic polymorphism ; Human genetics ; Natural killer cell lectin-like receptors ; NKG2C receptor
Publicado en:	Hla, Vol. 104, Issue 5 (November 2024) , art. e15764, ISSN 2059-2310

DOI: 10.1111/tan.15764
PMID: 39581700

11 p, 1.2 MB

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