Fc receptor

Fc receptors are membrane receptors for various immunoglobulin isotypes. All molecules except the FcRn receptor belong to the immunoglobulin superfamily. The name is based on the binding specificity of the receptors to a part of the C-terminus of an antibody called the Fc fragment (fragment crystallizable) and the constant region of an antibody. Fc receptors are glycosylated. This type of receptor is mainly produced by myeloid cells of the immune system. They are found on the surface of various immune cells, e.g. leukocytes, mast cells and others.

Keratinocytes also express Fc receptors (FcγRI, FcγRII and FcγRIII), among others. They also have complement receptors and mannose receptors, which enable them to attack a variety of microorganisms. Keratinocytes are therefore important modulators of the innate and adaptive immune response (Ali SM et al. 2013).

According to their affinity, Fc receptors can be divided into five subtypes, which are designated according to their bound immunoglobulin:

The Fcα receptor (CD89 ) binds the Fc domain of IgA. The receptor is found on the surface of monocytes, macrophages, neutrophils and eosinophils.

The Fcγ receptors bind the Fc domain of IgG. They are found on the surface of phagocytes, B lymphocytes, NK cells and dendritic cells. These receptors can recognize aggregated IgG molecules and bind them. The binding triggers different reactions depending on the cell type: e.g. opsonization or ADCC (by NK cells). There are different structural types of the Fcγ receptor:

• FcγRI(CD64)
• FcγRII(CD32)
• FcγRIII(CD16).

The Fcε receptors bind the Fc domain of free IgE. They are found on the surface of mast cells and basophilic granulocytes. Binding of antigens to these bound antibodies results in activation of the mast cell. This process plays a crucial role in type I allergy. Two types of Fcε receptors are distinguished (mammals) according to their affinity for IgE.

• FcεRI with high affinity
• FcεRII with low affinity to IgE.

Fcμ receptors bind the Fc domain of IgM.

Neonatal Fcγ receptor (FcRn) belongs to the MHC superfamily and binds IgG with weak affinity.

Note: TRIM21 binds Fc regions of IgG, IgA and IgM in the course of intracellular antibody-mediated degradation.

Bacterial Fc-binding proteins are protein A and protein G.

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3. Ochiai K et al. (2006) A review on Fc epsilon RI on human epidermal Langerhans cells [J]. International Archives of Allergy and Immunology 104 Suppl 1: 63-64.
4. Otten MA et al. (2004) The Fc receptor for IgA (FcalphaRI, CD89). Immunology Letters 92 (1-2): 23-31.
5. Ravetch JV et al. (1989) Alternative membrane forms of Fc gamma RIII (CD16) on human natural killer cells and neutrophils [J]. J Exp Med 170:481 - 497.