Spotlight on NKG2C and the human NK-cell response to CMV infection

Immune responses to cytomegalovirus (CMV) infection in the mouse and human involve the expansion of specific subsets of natural killer (NK) cells with specific phenotypic characteristics and a heightened ability to produce interferon (IFN)-gamma. In humans, these NK-cell responses are largely driven by the activating receptor NKG2C, which recognize human leukocyte antigen (HLA)-E in complex with leader sequence peptides. In this issue of the European Journal of Immunology, Noyola et al. [Eur. J. Immunol. 2012, 42: 3256-3266] examine NK-cell responses in a unique cohort of young children with asymptomatic and symptomatic congenital CMV infection. They also address NK-cell responses to CMV in relation to NKG2C gene copy number. Children with a symptomatic congenital infection exhibited a marked expansion of NKG2C(+) NK cells. However, despite having slightly lower frequencies of NKG2C(+) NK cells, children with a heterozygous deletion of the NKG2C gene seemed to control the virus as efficiently as those with two copies of the NKG2C gene. The present studies shed new light on the role of NKG2C copy number variation on the human NK-cell response to CMV infection.