tetano
Editor, Senior Moderator
Front Immunol. 2016 Sep 29;7:399. eCollection 2016.
[h=1]HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.[/h] Cox F[SUP]1[/SUP], Kwaks T[SUP]1[/SUP], Brandenburg B[SUP]1[/SUP], Koldijk MH[SUP]1[/SUP], Klaren V[SUP]1[/SUP], Smal B[SUP]1[/SUP], Korse HJ[SUP]1[/SUP], Geelen E[SUP]1[/SUP], Tettero L[SUP]1[/SUP], Zuijdgeest D[SUP]1[/SUP], Stoop EJ[SUP]1[/SUP], Saeland E[SUP]1[/SUP], Vogels R[SUP]1[/SUP], Friesen RH[SUP]1[/SUP], Koudstaal W[SUP]1[/SUP], Goudsmit J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] ADCC; CR6261; CR8033; CR9114; Fc-receptor; head-binding antibody; hemagglutinin; stem-binding antibody
PMID: 27746785 DOI: 10.3389/fimmu.2016.00399
[PubMed - in process] Free full text
[h=1]HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.[/h] Cox F[SUP]1[/SUP], Kwaks T[SUP]1[/SUP], Brandenburg B[SUP]1[/SUP], Koldijk MH[SUP]1[/SUP], Klaren V[SUP]1[/SUP], Smal B[SUP]1[/SUP], Korse HJ[SUP]1[/SUP], Geelen E[SUP]1[/SUP], Tettero L[SUP]1[/SUP], Zuijdgeest D[SUP]1[/SUP], Stoop EJ[SUP]1[/SUP], Saeland E[SUP]1[/SUP], Vogels R[SUP]1[/SUP], Friesen RH[SUP]1[/SUP], Koudstaal W[SUP]1[/SUP], Goudsmit J[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] ADCC; CR6261; CR8033; CR9114; Fc-receptor; head-binding antibody; hemagglutinin; stem-binding antibody
PMID: 27746785 DOI: 10.3389/fimmu.2016.00399
[PubMed - in process] Free full text