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Significance In addition to neutralizing antigens, antibodies are also capable of stimulating cellular responses through Fc–Fc receptor interactions. The type of response stimulated by these interactions is influenced by both the Fc receptor type expressed on the effector cell and the isotype of antibody to which it is bound. However, how antibody specificity influences Fc receptor functions, and how antibodies of different specificities interact to modulate these functions, remain unknown. Using influenza A virus as a model, we demonstrate that antibody specificity profoundly influences the induction of antibody-dependent cell-mediated cytotoxicity by effector cells. In addition, we show that interactions among antibodies that bind to discrete epitopes on the same antigen can influence the induction of Fc-dependent effector functions.

Epitope specificity plays a critical role in regulating antibody-dependent cell-mediated cytotoxicity against influenza A virus