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Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus
Cardiff Institute of Infection and Immunity, Cardiff University, Cardiff, CF14 4XN, UK
* Author to whom correspondence should be addressed.
Received: 31 October 2013; in revised form: 15 November 2013 / Accepted: 27 November 2013 / Published: 10 December 2013
Abstract: Human cytomegalovirus (HCMV) is an important pathogen that infects the majority of the population worldwide, yet, currently, there is no licensed vaccine. Despite HCMV encoding at least seven Natural Killer (NK) cell evasion genes, NK cells remain critical for the control of infection in vivo. Classically Antibody-Dependent Cellular Cytotoxicity (ADCC) is mediated by CD16, which is found on the surface of the NK cell in a complex with FcεRI-γ chains and/or CD3ζ chains. Ninety percent of NK cells express the Fc receptor CD16; thus, they have the potential to initiate ADCC. HCMV has a profound effect on the NK cell repertoire, such that up to 10-fold expansions of NKG2C+ cells can be seen in HCMV seropositive individuals. These NKG2C+ cells are reported to be FcεRI-γ deficient and possess variable levels of CD16+, yet have striking ADCC functions. A subset of HCMV cell surface proteins will induce robust antibody responses that could render cells susceptible to ADCC. We will consider how the strong anti-HCMV function of NKG2C+ FcεRI-γ-deficient NK cells could potentially be harnessed in the clinic to treat patients suffering from HCMV disease and in the development of an efficacious HCMV vaccine.
Keywords: HCMV; Cytomegalovirus; ADCC; antibody-dependent cellular cytotoxicity; NK cells; NKG2C; UL40; HLA-E; vaccine
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Aicheler, R.J.; Wang, E.C.Y.; Tomasec, P.; Wilkinson, G.W.G.; Stanton, R.J. Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus. Antibodies 2013, 2, 617-635.
Aicheler RJ, Wang ECY, Tomasec P, Wilkinson GWG, Stanton RJ. Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus. Antibodies. 2013; 2(4):617-635.
Aicheler, Rebecca J.; Wang, Eddie C.Y.; Tomasec, Peter; Wilkinson, Gavin W.G.; Stanton, Richard J. 2013. "Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of Human Cytomegalovirus." Antibodies 2, no. 4: 617-635.