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.

Abstract

Considerable effort has focused on the roles of the individual members of the FcγR receptor (FcγR) family in inflammatory diseases and humoral immunity. Recent work has revealed major roles in infection and in particular HIV pathogenesis and immunity. In addition, FcγR functions underpin the action of many of the successful therapeutic monoclonal antibodies. This emphasises the need for a greater understanding of FcγR 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 FcγR 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 FcγR receptor expression ensure there is much still to understand of the protective and deleterious effects of FcγRs in HIV infection. Careful comparative studies of human and non-human primate FcγRs will facilitate our appreciation of what attributes of HIV specific IgG antibodies, either acquired naturally or via vaccination, are most important for protection.