title: NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell compartment redistribution in response to human cytomegalovirus.
abstract: Human cytomegalovirus (HCMV) infection promotes a persistent expansion of a functionally competent NK-cell subset expressing the activating CD94/NKG2C receptor. Factors underlying the wide variability of this effect observed in HCMV-seropositive healthy individuals and exacerbated in immunocompromized patients are uncertain. A deletion of the NKG2C gene has been reported, and an apparent relation of NKG2C genotype with circulating NKG2C(+) NK-cell numbers was observed in HCMV(+) children. We have assessed the influence of NKG2C gene dose on the NK-cell repertoire in a cohort of young healthy adults (N = 130, median age 19 years). Our results revealed a relation of NKG2C copy number with surface receptor levels and with NKG2C(+) NK-cell numbers in HCMV(+) subjects, independently of HLA-E dimorphism. Functional studies showed quantitative differences in signaling (i.e. iCa(2+) influx), degranulation, and IL-15-dependent proliferation, in response to NKG2C engagement, between NK cells from NKG2C(+/+) and hemizygous subjects. These observations provide a mechanistic interpretation on the way the NKG2C genotype influences steady-state NKG2C(+) NK-cell numbers, further supporting an active involvement of the receptor in the HCMV-induced reconfiguration of the NK-cell compartment. The putative implications of NKG2C zygosity over viral control and other clinical variables deserve attention.
authors.affiliation: IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Aura
authors.initials: A
authors.lastname: Muntasell
authors.forename: María
authors.initials: M
authors.lastname: López-Montañés
authors.forename: Andrea
authors.initials: A
authors.lastname: Vera
authors.forename: Gemma
authors.initials: G
authors.lastname: Heredia
authors.forename: Neus
authors.initials: N
authors.lastname: Romo
authors.forename: Judith
authors.initials: J
authors.lastname: Peñafiel
authors.forename: Manuela
authors.initials: M
authors.lastname: Moraru
authors.forename: Joan
authors.initials: J
authors.lastname: Vila
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D000293:Adolescent; D000328:Adult; D020013:Calcium Signaling / Q000235:genetics / Q000276:immunology; D015550:Cell Degranulation / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology; D005260:Female; D018628:Gene Dosage; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D000097625:HLA-E Antigens; C569274:IL15 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human
keywords: CD94/NKG2C; Cytomegalovirus; Human; NK cells; NKG2C genotype