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.