Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact

SignificanceThe mechanism of how antiviral antibodies induce Fc–FcγR effector functions remains to be fully elucidated. Although the ability to activate effector functions is attributed to antibody isotype, this does not fully address why identical isotypes have different capabilities to stimulate effector function. We show that antibodies that target the influenza virus hemagglutinin (HA) require a second intermolecular interaction to optimally activate effector cells. We demonstrate that the receptor-binding domain of the HA is required to bind to sialic acid expressed on the surface of effector cells to optimize effector cell activation. This finding provides a basic understanding of how an optimal antibody-dependent cell-mediated response against influenza virus is achieved and may allow for better vaccine design.

Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact Journal Articles