What is Immunoglobulin ‘G’ (IgG)?

IgG is the major and most abundant immunoglobulin type in normal human serum. It constitutes about 70-75% of the total immunoglobulins and is about 8-16 mg/ml in serum. The heavy chains in this immunoglobulin are of gama (y) type and the light chains are either kappa or lambda type.

Molecular Weight of IgG is about 1, 46,000 daltons with 2 to 3% of carbohydrate content. Sedimentation co efficient of IgG is 7S. In general IgG is the major immunoglobulin secreted in secondary response.

The structure of IgG reflects the basic structure of immunoglobulin. When compared to the other immunoglobulins rate of production of IgG is high (about 33 mg/ Kg body weight/day) and their half life is about 23 days.

IgG is the only immnunoglobulin type that can cross the placental barrier to reach the fetus. Along with IgA secreted in the breast milk, residual IgG absorbed through the placenta provides immunity to the neonate prior to the establishment of its own immune system.

The passive protection provided by the maternal immunoglbulins remains up to 6 months soon after birth.

IgG antibodies are predominantly involved in the secondary antibody response, (the main antibody involved in primary response is IgM), thus IgG immunoglobulins presence generally corresponds to maturation of antibody response.

IgG can bind to many types of pathogens, such as viruses, bacteria, fungi etc. and provides protection against them through agglutination and immobilization, complement activation (classical pathway), opsonization for phagocytosis and neutralization of their toxins.

In humans the IgG class of immunoglobulins can be divided into four subclasses based on minor variations in the amino acid sequences of heavy chains. They are named as IgG IgG, IgG₃ and IgG₄ with reference to their abundance in serum.

Quantitatively, the relative serum concentrations of the human IgG subclasses are as follows IgG1 > IgG₂ > IgG₃ > IgG₄. The four subclasses show more than 95% homology in the amino acid sequences of the constant domains but, show most conspicuous differences in the amino acid composition and structure of the ‘hinge region.

The hinge region of IgG_: encompasses amino acids 216-231 and since it is freely flexible, the Fab fragments can rotate about their axes of symmetry and move within a sphere centered at the first of two inter-heavy chain disulfide bridges.

IgG₂has a shorter hinge than IgG, with 12 amino acid residues and four disulfide bridges. The hinge region of IgG₂ lacks a glycine residue; it is relatively short and contains a rigid poly-proline double helix, stabilized by extra inter-heavy chain disulfide bridges. These properties restrict the flexibility of the IgG₂ molecule. IgG₃ differs from the other subclasses by its unique extended hinge region (about four times as long as the IgG, hinge), containing 62 amino acids (including 21 prolines and 11 cysteines), forming an inflexible poly-proline double helix.

In IgG₃ the Fab fragments are relatively far away from the Fc fragment, giving the molecule a greater flexibility. The elongated hinge in IgG₃ is also responsible for its higher molecular weight compared to the other subclasses.

The hinge region of IgG₄ is shorter than that of IgGl and its flexibility is intermediate between that of IgG, and IgG_r All the subclasses except IgG, can cross placenta and provide protection to the baby.

The structural differences between the IgG subclasses are also reflected in their susceptibility to proteolytic enzymes, such as papain, plasmin trypsin and pepsin.

IgG₃ is very susceptible to cleavage by these enzymes, whereas IgG₂ is relatively resistant. IgG, and IgG₄ exhibit an intermediary sensitivity, depending upon the enzyme used.

As a consequence of the structural differences, the four IgG subclasses show differences in some of their physicochemical characteristics and biological properties also.