The FcγR of Humans and Non-human Primates and Their Interaction with IgG: Implications for Induction of Inflammation, Resistance to Infection and the Use of Therapeutic Monoclonal Antibodies

Considerable effort has focused on the roles of the individual members of the Fc gamma R receptor (Fc gamma R) family in inflammatory diseases and humoral immunity. Recent work has revealed major roles in infection and in particular HIV pathogenesis and immunity. In addition, Fc gamma R functions underpin the action of many of the successful therapeutic monoclonal antibodies. This emphasises the need for a greater understanding of Fc gamma R function in humans and in the NHP which provides a key model for human immunity and preclinical testing of antibodies. We discuss recent key aspects of the human Fc gamma R receptor biology and structure to define differences and similarities in activity between the human and macaque Fc receptors. These differences and similarities nuance the interpretation of infection and vaccine studies in the macaque. Indeed passive IgG antibody protection in lentivirus infection models in the macaque provided early evidence for the role of Fc receptors in anti-HIV immunity that have subsequently gained support from human vaccine trials. None-the-less the diverse functions and cellular contexts of Fc gamma R receptor expression ensure there is much still to understand of the protective and deleterious effects of Fc gamma Rs in HIV infection. Careful comparative studies of human and non-human primate Fc gamma Rs will facilitate our appreciation of what attributes of HIV specific IgG antibodies, either acquired naturally or via vaccination, are most important for protection.