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The many faces of FcγRI: implications for therapeutic antibody function
Author(s) -
Swisher Jennifer F. A.,
Feldman Gerald M.
Publication year - 2015
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12334
Subject(s) - avidity , cd64 , receptor , fc receptor , biology , signal transduction , microbiology and biotechnology , immunoreceptor tyrosine based activation motif , antibody , monoclonal antibody , context (archaeology) , immunology , immune system , phagocytosis , t cell receptor , t cell , biochemistry , paleontology
Summary Fcγ receptor I (Fcγ RI or CD 64) is the sole human Fc receptor with high affinity for monovalent IgG. While it contains an immunoreceptor tyrosine‐based activation motif in its cytoplasmic domain, binding of Fcγ RI can result in a complex array of activating and inhibitory outcomes. For instance, binding of monomeric IgG provides a low‐intensity tonic signal through Fcγ RI that is necessary for full interferon γ receptor signaling in the same cell. Interaction of Fcγ RI with larger high‐avidity complexes can result in phagocytosis, the generation of reactive oxygen species, as well as the synthesis and release of inflammatory cytokines. However, numerous reports also document potent anti‐inflammatory effects brought about by Fcγ RI engagement with immune complexes such as the inhibition of IFN γ and TLR 4 signaling, and secretion of interleukin‐10. This has led to conflicting hypotheses regarding the function of Fcγ RI , especially with regard to its role in the efficacy of several therapeutic monoclonal antibodies. While many of these issues are still unclear, continued characterization of the regulation and context dependence of Fcγ RI function, as well as the molecular mechanisms responsible for these various outcomes, will improve our understanding of Fcγ RI biology as well as the therapeutic strategies designed to harness or constrain its actions.