FceR1 FcεR1, high-affinity receptor for IgE
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Mast Cell
Basophil
Eosinophil
Monocyte
Langerhans Cell
5 / 15
25 / 70

Expression
FceRI is expressed on mast cells, basophils, eosinophils, monocytes, and Langerhans cells in the skin.

Structure
Fce RI is a heterotrimeric complex glycoprotein.  It is comprised of an a chain type 1 peptide, a b chain type 3, 3 span peptide and disulfide-linked g homodimer type 1 peptide.  In humans, but not the mouse, FceRI is thought to exist as both abg2 and complexes.  Fce RIa has an extracellular region composed of 2 IgSF domains followed by a highly conserved transmembrane region.  Within the transmembrane region a sequence of 9 aa conserved in human, rat and mouse, of which 8 residues are also identical in the CD16 transmembrane region.  FceRIb is a member of the CD20/FceRIb superfamily which includes CD20 and HTm4.  These molecules are predicted to have 4 transmembrane regions, cytoplasmic N- and C-termini, and short extracellular loops.  FceRIg is identical to the g subunit of CD16.  Fce RIg has an 86% aa identity between human, rat and mouse and is related to the z and h chains that are associated with the CD3/TCR complex.  The C-terminal cytoplasmic regions of FceRIb and FceRIg each contain an immunoreceptor tyrosine-based activation motif, ITAM.  FceRI shows no sequence similarity to the low-affinity IgE receptor CD23. 

MOLECULAR MASS
Cell Type Unreduced Reduced
a 45 - 65 kDa 45 - 65 kDa
b 27 kDa 27 kDa
g 20 kDa 7 - 10 kDa



Ligands
FceRIa  binds to monomeric IgE with a high affinity of kDa of 10 to the 10th M-1 and a stoichiometry of 1:1.  The binding site involves the 2nd IgSF-domain of FceRIa which interacts with the N-terminal segment of the Ce 3-domain of IgE.  The cytoplasmic tails of FceRIb and FceRIg associate noncovalently with the non-receptor protein tyrosine kinases Lyn and Syk, respectively.

Function
The high affinity receptor for IgE, FceRI on basophils and mast cells, plays a central role in allergic reactions. When a multi-valent allergen binds to FceRI-bound IgE, FceRI molecules are cross-linked and a signaling response is initiated.  The result is cellular degranulation, a rapid release of histamine and other stored mediators, and the secretion of pro-inflammatory cytokines.  These factors combine to induce the symptoms of immediate hypersensitivity. The a chain performs the ligand binding role by binding IgE, whereas the b chain serves to amplify signals that are transduced through the g  homodimer.  The function of FceRI on monocytes and Langerhans cells, in which the b chain is not expressed, is not clear, although FceRI on these cells is upregulated in atopic individuals.   On eosinophils, FceRI can mediate a cytotoxicity response against a metazoan parasite. The physiological role of FceRI in a normal immune response is thought to be in protection against parasites. The high affinity receptor for IgE, FceRI on basophils and mast cells plays a central role in allergic reactions. When a multi-valent allergen binds to FceRI-bound IgE, FceRI molecules are cross-linked and a signaling response is initiated. The result is cellular degranulation, a rapid release of histamine and other stored mediators, and the secretion of pro-inflammatory cytokines. These factors combine to induce the symptoms of immediate hypersensitivity. The a chain performs the ligand binding role by binding IgE, whereas the b chain serves to amplify signals that are transduced through the g homodimer. The function of Fce RI on monocytes and Langerhans cells, in which the b chain is not expressed, is not clear, although FceRI on these cells is upregulated in atopic individuals. On eosinophils, Fce RI can mediate a cytotoxicity response against a metazoan parasite. The physiological role of FceRI in a normal immune response is thought to be in protection against parasites.

Comments
The a and g genes of  FceRI are linked to other Fc receptor genes on chromosome 1.  A common variant of FceRIb, Ile181Leu within the 4th transmembrane region, shows a strong association with atopic IgE responses.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
MouseA34342P20489J05018
MouseB34342P20490J05019
MouseP20491J05020
RatA27116P12371M17153
RatA31231P13386M22923
RatS02118P20411
Antibodies

Revised June 25, 2008


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