Deciphering Fc-mediated Antiviral Antibody Functions in Animal Models

Schmaljohn, Alan L.; Orlandi, Chiara; Lewis, George K.

Fc-FcR affinity. We begin with a quote in a recent paper from the Ravetch group, leaders in the field of Fc-FcR interactions, and murine models with which to explore biological significance: "An antibody's Fc domain's relative affinity for the activating and inhibitory FcγR, called the A/I ratio, can determine its functional output, and is directly correlated to therapeutic efficacy in vivo. This has spawned recent efforts to engineer Abs with enhanced activating FcγR affinity." (26) Embedded in much of their work is the directly observed or implied importance not only of isotype (36) but also species matches in establishing Fc-FcR affinity: human, mouse, and non-human primate (NHP) FcR are non-equivalent in binding to any given Ab (typically, human IgG1 is the chosen type), and nomenclature of FcR in the various species is a poor guide to Ab affinity and function.