IgG antibody: Structure, Subclasses, Functions and Clinical Significance

This Antibody crosses placenta and play an important role in protecting the developing fetus.  If i can write only a single sentence to introduce IgG, the above sentence may be the most powerful sentence that represents IgG, but i am allowed to write a long boring (is it?) post. Hopefully you will find it useful. 

IgG is an important component of the neonatal immunological defense mechanisms against infection.

IgG is mostly found in the γ-globulin fraction (when separated into high-and low-molecular weight fractions, it is found in low-molecular-weight-fraction i.e. around 150,000 MW). Significant amounts of it and other classes of antibody molecules are found in the alpha and beta fraction of serum.

Schematic diagram of Immunoglobulin G (IgG) Source: Kuby Immunology

The intact 150,000-MW IgG molecule is, in fact, composed of subunits. Each IgG molecule contains two identical 50,000-MW polypeptide chains, designated as heavy (H) chains, and two identical 25,000-MW chains, designated as light (L) chains, which are linked by disulfide bridges.  Heavy chains of given antibody molecule determines the class (isotype) of that antibody, and IgG contains γ-heavy chains. Other antibody isotypes (class) are IgM (μ-Mu), IgA (α-Alpha), IgD (δ-Delta) and IgE (ε-Epsilon).

In humans, there are four subisotypes of γ heavy chains: γ1, γ2, γ3, and γ4 (therefore four subclasses, IgG1, IgG2, IgG3, and IgG4) which are numbered according to their decreasing average serum concentrations.

Heavy chains in IgA, IgD, and IgG contain three constant-region domains and a hinge region, whereas the heavy chains in IgE and IgM contain four constant-region domains and no hinge region.

Key Points Regarding IgG Antibodies

  1. Most abundant class in serum, constitutes about 80% of the total serum immunoglobulin.
  2. There are four Subclasses of IgG; IgG1, IgG2, IgG3, and IgG4
  3. Activates complement
  4. Crosses placenta and play an important role in protecting the developing fetus.

Functions of IgG Antibody

  1. Complement activation: Most IgG subclasses can activate complement system (It’s a collection of serum glycoproteins that can perforate cell membranes of pathogens).
  2. Antibody Dependent Cell-Mediated Cytotoxicity:
    NK cells express membrane receptor (CD16) for the carboxyl-terminal end (Fc region) of the IgG molecule. When an antigen/pathogens is coated with IgG antibody, NK cells can attach to these antibodies and subsequently destroy the targeted cells.
  3. Neonatal immunity: Some mammalian species, such as humans and mice, also transfer significant amounts of most subclasses of IgG from mother to fetus. The transfer of IgG from mother to fetus is a form of passive immunization (acquisition of immunity by receipt of preformed antibodies rather than by active production of antibodies after exposure to antigen).
  4. Opsonization
  5. Feedback inhibition of B Cells

Sub-classes of IgG

If you want to have in-depth information about IgG sub-classes you can also read about sub-classes of IgG.

General Structure of Four Subclasses of IgG Antibody
General Structure of Four Subclasses of IgG Antibody (Source: Kuby Immunology)

Four subclasses of human IgG differ in their structure because they are encoded by different germ-line CH genes.  They differ in the size of the hinge region and the number and arrangements of the interchain disulfide bonds linking their heavy chains. A notable feature of human IgG3 is its 11 interchain disulfide bonds.

This subtle differences in the amino acid sequence between subclasses of IgG also affects its biological functions:

  • IgG1, IgG3, and IgG4 readily cross the placenta but IgG2 crosses the placenta with much lower efficiency
  • IgG3 is the most effective complement activator, followed by IgG1; IgG2 is less efficient, and IgG4 is not able to activate complement at all.
  • IgG1 and IgG3 bind with high affinity to Fc receptors on phagocytic cells and thus mediate opsonization. IgG4 has an intermediate affinity for Fc receptors, and IgG2 has an extremely low affinity.
About tankeshwar 371 Articles
Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion, I am working as a Asst. Professor and Microbiologist at Department of Microbiology and Immunology, Patan Academy of Health Sciences, Nepal. If you want me to write about any posts that you found confusing/difficult, please mention in the comments below.

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