Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab-Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mecha...

The avian IgY antibody isotype shares a common ancestor with both mammalian IgG and IgE and so provides a means to study the evolution of their structural and functional specialisations. Although both IgG and IgE bind to their leukocyte Fc receptors with 1:1 stoichiometry, IgY binds to CHIR-AB1, a receptor expressed in avian monocytes, with 2:1 stoichiometry. The mutagenesis data reported here ...

The IgE (immunoglobulin E) receptor of cultured rat basophilic leukemia (RBL-1) cells, shown previously to be an M, = 45,000 to 50,000 glycoprotein, was purified by repetitive affinity chromatography on IgE-Sepharose. RBL-1 cells were either labeled exogenously with “‘1 by the lactoperoxidase method or endogenously by growing cells in the presence of o-[14C]glucosamine and L-[3H]leucine. Recept...

Asthma is a disease characterized by spontaneous contraction of the airways in response to a wide variety of endogenous and exogenous stimuli. Many asthma models are used to mimic the human asthma model in the literature. In order to better understand the role of the cannabinoid (CB) 2 receptor in the ovalbumin (OVA)-induced asthma model, a combination of both selective CB2 agonist (AM1241) and...

Immunoglobulin (Ig)E-mediated activation of mast cells has long been thought to occur only when Fc(epsilon)RI receptor-bound IgE is cross-linked via multivalent antigens. However, recent studies have raised the possibility that mast cells may be activated by the binding of IgE to the Fc(epsilon)RI receptor in the absence of antigen. Here we demonstrate that IgE binding without antigen induces t...

Polymorphonuclear neutrophils (PMNs) are important effector cells in host defense and the inflammatory response to antigen. The involvement of PMNs in inflammation is mediated mainly by the Fc receptor family, including IgE receptors. Recently, PMNs were shown to express two IgE receptors (CD23/Fc«RII and galectin-3). In allergic diseases, the dominant role of IgE has been mainly ascribed to it...

We have recently shown that small oligomers of IgE bound to univalent receptors for IgE on the surface of rat basophilic leukemia cells induce extensive aggregation of the receptors at 4 degrees C into patches resolvable by fluorescence microscopy and that this does not occur with monomeric IgE (Menon, A. K., D. Holowka, and B. Baird, 1984, J. Cell Biol. 98:577-583). Here we use fluorescence ph...

Immunoglobulin E (IgE) induces mast cell survival in the absence of antigen (Ag) through the high-affinity IgE receptor, Fcepsilon receptor I (FcepsilonRI). Although we have shown that protein tyrosine kinase Syk and sustained extracellular signal-regulated kinase (Erk) activation are required for IgE-induced mast cell survival, how Syk couples with sustained Erk activation is still unclear. He...

Immunoglobulin E (IgE) plays a central role in the pathogenesis of immediate hypersensitivity reactions because of its capacity to bind specifically to high-affinity IgE receptors on mast cells or basophiles by the alpha chain of Fc epsilon receptor type I (Fc-epsilon RI-α).1 In addition to its ability to activate mast calls and basophiles, IgE can bind to the low-affinity IgE receptor (CD23, o...

The high-affinity receptor for immunoglobulin (Ig) E (Fc epsilon RI) on mast cells and basophils plays a key role in IgE-mediated allergies. Fc epsilon RI is composed of one alpha, one beta, and two gamma chains, which are all required for cell surface expression of Fc epsilon RI, but only the alpha chain is involved in the binding to IgE. Fc epsilon RI-IgE interaction is highly species specifi...