Dataset Information

HA Antibody-Mediated Fc?RIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

ABSTRACT: Interactions with receptors for the Fc region of IgG (Fc?Rs) have been shown to contribute to the in vivo protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated Fc?RIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate Fc?RIIIa activation. However, the Fc?RIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with Fc?RIIIa activation. The inhibition of Fc?RIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-Fc?R binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

SUBMITTER: Cox F

PROVIDER: S-EPMC5040702 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

Cox Freek F Kwaks Ted T Brandenburg Boerries B Koldijk Martin H MH Klaren Vincent V Smal Bastiaan B Korse Hans J W M HJ Geelen Eric E Tettero Lisanne L Zuijdgeest David D Stoop Esther J M EJ Saeland Eirikur E Vogels Ronald R Friesen Robert H E RH Koudstaal Wouter W Goudsmit Jaap J

Frontiers in immunology 20160929

Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the <i>in vivo</i> protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-b ...[more]

PMID: 27746785

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Dataset Information

HA Antibody-Mediated Fc?RIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

Publications

HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

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