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: Aura Muntasell, María López-Montañés, Andrea Vera, Gemma Heredia, Neus Romo, Judith Peñafiel, Manuela Moraru, Joan Vila, Carlos Vilches, Miguel López-Botet
• Journal: European journal of immunology (Eur J Immunol) Vol. 43 Issue 12 Pg. 3268-78 (Dec 2013) ISSN: 1521-4141 [Electronic] Germany
• PMID: 24030638 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• HLA-E antigen
• Histocompatibility Antigens Class I
• IL15 protein, human
• Interleukin-15
• KLRC2 protein, human
• KLRD1 protein, human
• NK Cell Lectin-Like Receptor Subfamily C
• NK Cell Lectin-Like Receptor Subfamily D

Topics

• Adolescent
• Adult
• Calcium Signaling (genetics, immunology)
• Cell Degranulation (genetics, immunology)
• Child
• Child, Preschool
• Cytomegalovirus (genetics, immunology)
• Cytomegalovirus Infections (genetics, immunology)
• Female
• Gene Dosage
• Histocompatibility Antigens Class I (genetics, immunology)
• Humans
• Interleukin-15 (genetics, immunology)
• Killer Cells, Natural (immunology)
• Male
• NK Cell Lectin-Like Receptor Subfamily C (genetics, immunology)
• NK Cell Lectin-Like Receptor Subfamily D (genetics, immunology)