**3.1 Human Fcγ receptors**

Human Fcγ receptors comprise a family of glycoproteins expressed on the membrane of immune cells [7, 8]. These receptors can bind to the various IgG subclasses with different affinities [7], and induce different cellular responses [6]. FcγR can be classified as activating receptors (FcγRI/CD64, FcγRIIa/CD32a, FcγRIIIa/CD16a, and FcγRIIIb/CD16b), and one inhibitory receptor (FcγRIIb/CD32b) [7, 9, 33, 34] (**Figure 3**).

FcγRI is a high affinity receptor, having three Ig-like extracellular domains. It binds mainly monomeric IgG [9]. In contrast, FcγRII and FcγRIII are low-affinity receptors, having two Ig-like extracellular domains. They bind only multimeric immune complexes [9, 35]. FcγRI is associated with a dimer of the common Fc receptor γ chain, which contains an immunoreceptor tyrosine-based activation motif (ITAM) sequence (**Figure 3**). The ITAM sequence is important for receptor signaling [36].

FcγRIIa contains its own ITAM within its cytoplasmic tail. In contrast, the inhibitory receptor FcγRIIb contains an immunoreceptor tyrosine-based inhibition

#### **Figure 3.**

*Human Fcγ receptors. Schematic illustration of human receptors for IgG. Fcγ receptors are shown relative to the cell membrane (brown line). The IgG-binding chain (α) is expressed together with their respective γ2 signaling subunits. FcγRI is a high affinity receptor, having three Ig-like extracellular domains. FcγRII and FcγRIII are low-affinity receptors, having two Ig-like extracellular domains. FcγRIIIb is expressed exclusively on neutrophils, and it is a glycosylphosphatidylinositol (GPI)-linked receptor missing a cytoplasmic tail. ITAM, immunoreceptor tyrosine-based activation motif with consensus sequence YxxI/Lx (6–12)YxxI/L [36] (green oval); ITIM, immunoreceptor tyrosine-based inhibitory motif with the consensus sequence I/V/L/SxYxxL/V [39] (red oval).*

#### *Neutrophils*

motif (ITIM) within its cytoplasmic tail (**Figure 3**). The FcγRIIb negatively regulates various cell functions including antibody production by the B cell [37], proliferation, degranulation, and phagocytosis in other leukocytes when it is crosslinked with activating FcγRs [38, 39]. Most leukocytes express both activating and inhibitory FcγRs, hence simultaneous cross-linking establishes a threshold for cell activation [40] that maintains a balanced immune response [41, 42].

FcγRIII has two isoforms: FcγRIIIa is a receptor with a transmembrane domain and a cytoplasmic tail, associated with an ITAM-containing homodimer of Fc receptor γ chains (**Figure 3**). It is expressed mainly on macrophages, natural killer (NK) cells, and dendritic cells [7, 8]. In contrast, FcγRIIIb is expressed exclusively on neutrophils and it is a glycosylphosphatidylinositol (GPI)-linked receptor missing a cytoplasmic tail. Also, no other subunits are known to associate with it (**Figure 3**). It is important to mention that human FcγRIIa and FcγRIIIb are exclusive receptors that are not found in other species [33, 43].
