IMGT Lexique

Fc Receptors (FcR)

Fc receptors play a major role in immune defenses against pathogens and in inflammatory processes.

Because of their ability to bind the Fc portion of antibodies, Fc receptors provide a link between humoral and cellular immune responses. There are Fc receptors for each Ig isotype.

Functions

FcRs fall into two general classes: those involved in effector functions and those that transport immunoglobulins across epithelial barriers.

Structure

Except for FcΕRII (CD23), which is C-type lectin-like, all other known Fc receptors are members of the immunoglobulin superfamily [1].

Affinity

FcγRI and FcΕRI are high-affinity receptors with dissociation constants ranging from 10^-8 to 10^-10 M, whereas the other receptors, such as FcγRII and FcγRIII, are low-affinity receptors with dissociation constants ranging from 10^-5 to 10^-7.

FcγRIIB (CD32), the low-affinity receptor for the Fc fragment of IgG, is expressed on almost all hematopoietic cells, including B lymphocytes, NK KIR*cells,etc.

Fcγ receptors (FcγR)
There are two major classes of Fcγ receptors: receptors that activate effector functions and receptors that inhibit these functions.
FcRs that mediate phagocytosis in human macrophages fall within the activation class and include Fcγ RI, Fcγ RIIA, and Fcγ RIII.
FcγRIII, also known as CD16, is the type III Fcγ receptor. It exists, as two isoforms in humans, FcγRIIIa and FcγRIIIb, sharing 96% sequence identity in their extra-cellular immunoglobulin binding regions. FcγRIIIa is expressed on macrophages, mast cells, and natural killer cells as a transmembrane receptor. Present exclusively on neutrophils, FcγRIIIb is the only Fc receptor anchored by a glycosyl-phosphatidylinositol (GPI) linker to the plasma membrane. Despite the lack of a signaling component, FcγRIIIb plays an active role in triggering Ca²⁺ mobilization and neutrophil degranulation. In addition, in conjunction with FcγRIIIa, FcγRIIIb activates phagocytosis, degranulation, and oxidative burst, which lead to the clearance of opsonized pathogens by neutrophils. A soluble form of FcγRIIIb activates the complement receptor CR3-dependent inflammatory process. The immunoglobulin binding affinities of FcγRIIIb were reported to be 1 x 10^-6 and 2 x 10^-6 M for human IgG1 and IgG3, respectively.
Fcε receptors (FcεR)
IgE binds three types of IgE receptors, the high-affinity IgE receptor (FcεRI) on basophils and mast cells, the low-affinity IgE receptor (Fcε RII or CD23), and the galectin 3 (gal 3) through contact sites within the CH2 and CH3 domains or carbohydrate moieties.

3D structures

The recent crystal structures of a human FcΕRIa [2], FcγRIIa [3], FcγRIIb [4] and FcγRIII [5] revealed a conserved immunoglobulin-like (Ig-like) structure, particularly the small hinge angle between the two Ig-like domains, that is unique to the Fc receptors.

[1]	Daëron, M. (1997) Annu. Rev. Immunol. 15, 203-234.
[2]	Garman, S. C. et al. (1998) Cell 95, 951-961.
[3]	Maxwell, K. F. et al. (1999) Nat. Struct. Biol. 6, 437-442.
[4]	Sondermann, P. et al. (1999) EMBO J. 18, 1095-1103.
[5]	Zhang, Y. et al. (2000) Immunity 13, 387-395.