Immunoglobulin G



Immunoglobulin G (IgG) are antibody molecules. Each IgG is composed of four peptide chains -- two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other Immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.

IgG is the most abundant immunoglobulin and is approximately equally distributed in blood and in tissue liquids, constituting 75% of serum immunoglobulins in humans. IgG molecules are synthesized and secreted by plasma B cells.

Functions
IgG antibodies are predominantly involved in the secondary immune response (the main antibody involved in primary response is IgM). The presence of specific IgG generally corresponds to maturation of the antibody response.

IgG is the only isotype that can pass through the human placenta, thereby providing protection to the fetus in utero. Along with IgA secreted in the breast milk, residual IgG absorbed through the placenta provides the neonate with humoral immunity before its own immune system develops. Colostrum contains a high percentage of IgG, especially in bovine  colostrum.

IgG can bind to many kinds of pathogens, for example viruses, bacteria, and fungi, and protects the body against them by agglutination and immobilization, complement activation (classical pathway), opsonization for phagocytosis and neutralization of their toxins. It also plays an important role in Antibody-dependent cell-mediated cytotoxicity(ADCC).

IgG is also associated with Type II and Type III Hypersensitivity.

Structure
IgG antibodies are large molecules of about 150 kDa composed of 4 peptide chains. It contains 2 identical heavy chains of about 50 kDa and 2 identical light chains of about 25 kDa, thus tetrameric quaternary structure. The two heavy chains are linked to each other and to a light chain each by disulfide bonds. The resulting tetramer has two identical halves which together form the Y-like shape. Each end of the fork contains an identical antigen binding site. The Fc regions of IgGs bear a highly conserved N-glycosylation site. The N-glycans attached to this site are predominantly core-fucosylated diantennary structures of the complex type. Additionally, small amounts of these N-glycans also bear bisecting GlcNAc and α-2,6 linked sialic acids residues.

Subclasses
There are four IgG subclasses (IgG1, 2, 3 and 4) in humans, named in order of their abundance in serum (IgG1 being the most abundant).

Note: IgG affinity to Fc receptors on phagocytic cells is specific to individual species from which the antibody comes as well as the class. The structure of the hinge regions gives each of the 4 IgG classes their unique biological profile. Even though there is about 95% similarity between their Fc regions, the structure of the hinge regions are relatively different.

Receptors
In humans, the three receptors for IgG are:

FcγRI (CD64) – 72kDa in size. Expressed on cells of mononuclear phagocyte lineage.

FcγRII (CD32) – 40kDa in size. Has 2 forms, alpha (with an ITAM receptor motif) and beta (with an ITIM receptor motif).

FcγRIII (CD16) – 50-80kDa in size. Has 2 forms, alpha (a transmembrane protein) and beta (expressed on neutrophils).

Glycosylation is essential for IgG binding to its receptors, regardless of its class.