Type II Fc receptor (Type II FcR)

Type II Fc receptors are a specialized group of receptors that recognize the Fc portion of antibodies, distinguished from classical Type I receptors by their C-type lectin domain and their binding to the closed conformation of the Fc region (Pincetic et al., 2014). This class includes CD23 (FcεRII), which regulates IgE levels and B-cell functions, and DC-SIGN (CD209), which interacts with specific IgG glycoforms to mediate anti-inflammatory effects (Anthony & Ravetch, 2010). Unlike Type I receptors that often trigger pro-inflammatory responses like phagocytosis and ADCC, Type II receptors are primarily involved in immune homeostasis and the modulation of inflammation. They are significant therapeutic targets in the treatment of allergic diseases, asthma, and autoimmune conditions. For example, the drug lumiliximab targets CD23 to treat chronic lymphocytic leukemia and has been explored for asthma, while intravenous immunoglobulin (IVIG) is believed to exert its systemic anti-inflammatory benefits through Type II receptor pathways. Understanding the structural biology and glycan-dependency of these receptors is vital for designing antibodies with tailored effector functions and improved safety profiles.

Other names

Non-classical Fc receptorsC-type lectin Fc receptorsCD23FcεRIIDC-SIGNCD209FCER2CLEC4L

Modulation of B-cell signaling and IgE production via CD23; induction of IL-10 and anti-inflammatory cascades via DC-SIGN binding of sialylated IgG (Anthony & Ravetch, 2010; Pincetic et al., 2014).