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Inhibitory receptors have been proposed to modulate the in vivo cytotoxic response against tumor targets for both spontaneous and antibody-dependent pathways. Using a variety of syngenic and xenograft models, we demonstrate here that the inhibitory FcgammaRIIB molecule is a potent regulator of antibody-dependent cell-mediated cytotoxicity in vivo,(More)
In addition to their role in binding antigen, antibodies can regulate immune responses through interacting with Fc receptors (FcRs). In recent years, significant progress has been made in understanding the mechanisms that regulate the activity of IgG antibodies in vivo. In this Review, we discuss recent studies addressing the multifaceted roles of FcRs for(More)
The gamma subunit of immunoglobulin Fc receptors is an essential component of the high-affinity receptor for IgG (Fc gamma RIII) and is associated with the high-affinity receptor for IgG (Fc gamma RI) and the T cell receptor-CD3 complex. It is required for both receptor assembly and signal transduction. Targeted disruption of this subunit results in(More)
Since the description of the first mouse knockout for an IgG Fc receptor seven years ago, considerable progress has been made in defining the in vivo functions of these receptors in diverse biological systems. The role of activating Fc gamma Rs in providing a critical link between ligands and effector cells in type II and type III inflammation is now well(More)
Immunoglobulin G (IgG) mediates pro- and anti-inflammatory activities through the engagement of its Fc fragment (Fc) with distinct Fcg receptors (FcgRs). One class of Fc-FcgR interactions generates pro-inflammatory effects of immune complexes and cytotoxic antibodies. In contrast, therapeutic intravenous gamma globulin and its Fc fragments are(More)
Interferons are a family of proteins first identified by their ability to induce cellular resistance to infection by many viruses. In addition to the antiviral properties it shares with the alpha- and beta-interferons, gamma-interferon (IFN-gamma), a lymphokine secreted by activated T cells, activates macrophages, stimulates B cells, increases fibroblast(More)
Dendritic cells (DCs) have the capacity to initiate immune responses, but it has been postulated that they may also be involved in inducing peripheral tolerance. To examine the function of DCs in the steady state we devised an antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted(More)
Recent advances in the structural analysis of the genes and proteins for immunoglobulin Fc domain receptors have provided a molecular characterization of this complex family. The wide cellular distribution of these receptors and their functional heterogeneity are reflected in the diversity of molecules which bind antibody and immune complexes. The detailed(More)
Immune complexes are potent activators of inflammatory cells, triggering effector responses through the crosslinking of Fc receptors (FcRs) such as Fc(epsilon)RI or Fc(gamma)RIII. On B cells and mast cells, immune complexes are also negative regulators of activation triggered by antigen and Fc receptors, a consequence of coligation of the B-cell antigen(More)
CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, is expressed on antigen-presenting cells (APCs) and is essential for immune activation. Although agonistic CD40 antibodies have been developed for immunotherapy, their clinical efficacy has been limited. We have found that coengagement of the Fc domain of agonistic CD40 monoclonal(More)