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EBioMedicine. 2016 Jun;8:277-290. doi: 10.1016/j.ebiom.2016.04.029. Epub 2016 Apr 28.

What Lies Beneath: Antibody Dependent Natural Killer Cell Activation by Antibodies to Internal Influenza Virus Proteins.

Author information

1
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
2
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Seqirus Ltd, Parkville, Australia.
3
WHO Collaborating Centre for Reference and Research on Influenza at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
4
La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, Bundoora, Australia.
5
Burnet Institute, Melbourne, Australia.
6
Jenner Institute, Oxford University, Oxford, UK.
7
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia; Melbourne Sexual Health Centre, Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Parkville, Australia. Electronic address: skent@unimelb.edu.au.

Abstract

The conserved internal influenza proteins nucleoprotein (NP) and matrix 1 (M1) are well characterised for T cell immunity, but whether they also elicit functional antibodies capable of activating natural killer (NK) cells has not been explored. We studied NP and M1-specific ADCC activity using biochemical, NK cell activation and killing assays with plasma from healthy and influenza-infected subjects. Healthy adults had antibodies to M1 and NP capable of binding dimeric FcγRIIIa and activating NK cells. Natural symptomatic and experimental influenza infections resulted in a rise in antibody dependent NK cell activation post-infection to the hemagglutinin of the infecting strain, but changes in NK cell activation to M1 and NP were variable. Although antibody dependent killing of target cells infected with vaccinia viruses expressing internal influenza proteins was not detected, opsonising antibodies to NP and M1 likely contribute to an antiviral microenvironment by stimulating innate immune cells to secrete cytokines early in infection. We conclude that effector cell activating antibodies to conserved internal influenza proteins are common in healthy and influenza-infected adults. Given the significance of such antibodies in animal models of heterologous influenza infection, the definition of their importance and mechanism of action in human immunity to influenza is essential.

KEYWORDS:

Antibody dependent cellular cytotoxicity; Hemagglutinin; Influenza; Matrix protein 1; Natural killer cells; Nucleoprotein

PMID:
27428437
PMCID:
PMC4919476
DOI:
10.1016/j.ebiom.2016.04.029
[Indexed for MEDLINE]
Free PMC Article

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