IgE Receptors

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IgE is known as the main antibody involved in allergic inflammatory processes such as asthma, atopic dermatitis, and allergic rhinitis. Two distinct receptors have been demonstrated for IgE: the high-affinity IgE receptor (FceRI), and the low-affinity IgE receptor (FceRII).

In humans, the high-affinity receptor has two forms: the "classical" tetrameric FceRI (aj3y2), which is constitutively expressed on effector cells of anaphylaxis (mast cells, basophils), and the trimeric form (ay2), which is variably expressed on APCs such as monocytes, DCs, and LCs (15). This minimal structure enables APCs to efficiently take up and present antigen in IgE-mediated, delayed-type hypersensitivity reactions that are thought to play an important role in atopic disease. However, the FceRI in the trimeric form shows much lower density of surface expression and a reduced stability of the receptor protein complexes (16). The a chain of FceRI is responsible for IgE binding and is a member of the immunoglobulin superfamily (17). The four transmembrane domain ¡3 chain increases stability and signaling capacity as well as augmenting the maturation of the a chain and its intracellular trafficking to the cell surface, and the dimer of the signal-transducing y chain, which is shared by other Fc receptor complexes, carries two immunoreceptor tyrosine-based activation motifs (ITAMs) and is mandatory for the surface expression of the heterotrimeric structure (16,18).

Consequent to expressing the FceRI ay2 form of receptor, APCs show an intracellular accumulation of the a chain, which is presumably caused by the slower maturation and transport process due to the absence of the ¡ chain. Again, consequent to the absence of the ¡ chain, signals transducted by the trimeric receptor are 3-5 times weaker than those mediated by the tetrameric receptor (16). The absence of the ¡ chain indicates that it is not related to the capacity of DCs and LCs to respond to FceRI mediated activation.

Human FceRII (known as CD23) is a Ca+2 dependant type C-lectin and exists in two forms: CD23a, which is constitutively expressed in B cells and is associated with endocytosis of IgE-coated particles; and CD23b, which is induced in particular by IL-4, is found also on non B-cells such as T cells, monocytes, macrophages, platelets, and eosinophils. The pathophysiological role of this receptor on APCs in relation to allergy remains to be revealed. It may well be involved in antigen uptake and presentation like the FceRI receptor in atopic patients, but because of its low affinity for monomeric IgE, it has been assumed that this receptor is involved in the binding of IgE-antigen complexes (1).

In atopic individuals, recent studies have shown that FceRI is the main serum IgE-binding structure on APCs and allows these cells to endocytose IgE-complexed allergen with high efficiency, thereby enabling the threshold dose of allergen required to activate allergen-specific TH cells to be 100-1000x lower than the dose required for uncomplexed allergen or for nonatopic DCs (9). Hence, antigens are more efficiently taken up, processed, and presented to T cells after targeting to the APC via FceRI as compared with allergen binding to APC in the conventional manner. After polyvalent ligation, the FceRI-bound IgE is internalized into acidic proteolytic compartments where it is degraded before delivery to organelles containing MHC class II (16).

The binding of an allergen to the complex of IgE-FceRI and the associated cross-linking of these receptors on FceRI-bearing cells leads to the rapid activation and release of inflammatory mediators and the production of a variety of cytokines by APCs. Observations in atopic dermatitis (AD) patients have shown that this resultant cytokine production by the aggregation of surface FceRI may preferentially induce a TH2 type of cell activation (17,19).

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