3.2 FcεRI – structure and function on effector cells and APCs
The high-affinity IgE receptor (FcεRI) is a member of the immunoglobulin (Ig) superfamily. It is highly expressed as an αβγ2 tetramer (~200,000 molecules/cell) on the surface of mast cells and basophils35,36
It consists of four polypeptide chains, an α chain, a β chain and two disulfide-linked γ chains37(Saini et al.,2001). In human monocytes, Langerhans” cells and peripheral blood DCs, eosinophils, platelets and smooth-muscle cells, FcεRI is expressed as a αγ2 trimer, consisting of one α and two γ chains3,38. The α chain consists of an extracellular domain, a single transmembrane helix domain and a short cytoplasmic sequence. The IgE binding function of the high-affinity IgE receptor is confined to the two extracellular domains of the α chain, with a 1:1 binding stoichiometry. Both intracellular sequences of the β and γ chains consist of immunoreceptor tyrosine-based activation motifs (ITAMs). The β subunit chain functions as an amplifier of downstream events after the initial activation of surface FcεRI37 (Saini et al., 2001). The lack of a β chain may account for the variable expression of this receptor on certain cells. Cross-linking of tetrameric FcεRI on the surface of mast cells and basophils leads to cellular activation, resulting in degranulation and the release of preformed mediators, synthesis of lipid mediators and the release of inflammatory cytokines, leading to the recruitment of leukocytes which further enhance the allergic response39. IgE enhances the expression of FcεRI by stabilization of the receptor40,41, and occupancy of FcεRI can also prolong mast cell survival by IgE42
The trimeric expression of FcεRI on monocytes, DCs and Langerhans cells has been shown to facilitate allergen presentation to CD4+ T cells. The efficiency of FcεRI-mediated allergen uptake by antigen-presenting cells (APCs) is 100 to 1000-fold more effective than any endocytosis or pinocytosis17,43. FcεRI is up-regulated by mast cells in seasonal allergic rhinitis and its expression correlates with serum IgE concentrations44-47.