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

Autor:	Cox F; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Kwaks T; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Brandenburg B; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Koldijk MH; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Klaren V; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Smal B; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Korse HJ; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Geelen E; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Tettero L; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Zuijdgeest D; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Stoop EJ; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Saeland E; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Vogels R; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Friesen RH; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Koudstaal W; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands., Goudsmit J; Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2016 Sep 29; Vol. 7, pp. 399. Date of Electronic Publication: 2016 Sep 29 (Print Publication: 2016).
DOI:	10.3389/fimmu.2016.00399
Abstrakt:	Interactions with receptors for the Fc region of IgG (FcγRs) 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 FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa 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 FcγRIIIa activation. The inhibition of FcγRIIIa 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-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.
Databáze:	MEDLINE
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