Fcγ receptor pathways during active and passive immunization.
IgG antibodies are actively produced in response to antigenic challenge or passively administered as an effective form of immunotherapy to confer immunity against foreign antigens. Their protective activity is mediated through their bifunctional nature: a variable Fab domain mediates antigen-binding specificity, whereas the constant Fc domain engages Fcγ receptors (FcγRs) expressed on the surface of leukocytes to mediate effector functions. While traditionally considered the invariant domain of an IgG molecule, the Fc domain displays remarkable structural heterogeneity determined primarily by differences in the amino acid sequence of the various IgG subclasses and by the composition of the complex, Fc-associated biantennary N-linked glycan. These structural determinants regulate the conformational flexibility of the IgG Fc domain and affect its capacity to interact with distinct types of FcγRs (type I or type II FcγRs). FcγR engagement activates diverse downstream immunomodulatory pathways with pleiotropic functional consequences including cytotoxicity and phagocytosis of IgG-coated targets, differentiation and activation of antigen presenting cells, modulation of T-cell activation, plasma cell survival, and regulation of antibody responses. These functions highlight the importance of FcγR-mediated pathways in the modulation of adaptive immune responses and suggest a central role for IgG-FcγR interactions during active and passive immunization.
The Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
Stylianos
S
Bournazos
The Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, USA.
Jeffrey V
JV
Ravetch
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000737:chemistry / Q000145:classification / Q000276:immunology* / Q000378:metabolism*; D056747:Immunomodulation; D007167:Immunotherapy; D005810:Multigene Family; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017452:Receptors, IgG / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014611:Vaccination
D007074:Immunoglobulin G; D017452:Receptors, IgG
Fc receptors; antibodies; immunotherapies; inflammation; vaccination