What lies beneath: antibody dependent natural killer cell activation by antibodies to internal influenza virus proteins

Vanderven, Hillary A., Ana-Sosa-Batiz, Fernanda, Jegaskanda, Sinthujan, Rockman, Steven, Laurie, Karen, Barr, Ian, Chen, Weisan, Wines, Bruce, Hogarth, P. Mark, Lambe, Teresa, Gilbert, Sarah C., Parsons, Matthew S., and Kent, Stephen J. (2016) What lies beneath: antibody dependent natural killer cell activation by antibodies to internal influenza virus proteins. EBioMedicine, 8. pp. 277-290.

[img]
Preview
PDF (Published Version) - Published Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (1MB) | Preview
View at Publisher Website: http://dx.doi.org/10.1016/j.ebiom.2016.0...
 
28
34


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 Fc gamma RIIIa 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.

Item ID: 56888
Item Type: Article (Research - C1)
ISSN: 2352-3964
Keywords: Influenza, Natural killer cells, Antibody dependent cellular cytotoxicity, Nucleoprotein, Matrix protein 1, Hemagglutinin
Copyright Information: © 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Date Deposited: 16 Jan 2019 07:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
Downloads: Total: 34
Last 12 Months: 17
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page