Diversity and duplicity: Human Fcγ receptors in host defense and autoimmunity

Given the central role of Ig in bridging the innate and acquired immune systems through both the affector and effector arms, it is not surprising that receptors for Ig play an important role in immune function. Strategies to block their function have been developed by microbial pathogens, and evolution has endowed humans with a diverse set of physiologically relevant receptor variants, presumably to allow fine tuning of the immune response. At least several of these variants appear to be risk factors for autoimmune disease, and they demonstrate the importance of more subtle variation in structure and function. These observations may assist in guiding the engineering of MAbs and Fc-fusion proteins for more effective Ig-based therapeutics.