Immunoglobulins (Antibodies) Structure and Classes

Immunoglobulins, also known as antibodies, are special types of glycoprotein molecules that are secreted by well-differentiated B cells, called plasma cells. Antibodies specifically react with the antigens which stimulated their production. They are released from lymph nodes and spleen into the blood where they serve as the effector of humoral immunity.

Antibodies are part of the serum proteins and are found in the gamma (γ) globulin fraction if serum proteins are separated by electrophoresis so also called immunoglobulins.

Basic Structure of an Immunoglobulin

Basic Structure of antibody molecule

Antibodies are Y-shaped tetra-peptide molecules consisting of two identical heavy (H) chains and two identical light (L) chains, held together by disulfide bonds. Each light chain is bound to a heavy chain by a disulfide bond to form a heterodimer (H-L). Two identical heavy and light (H-L) chain combinations are also held together by disulfide bridges forming a basic four-chain (H-L)2 antibody structure, a dimer of dimers. The exact number and precise locations of these interchain disulfide bonds differ among antibody classes and subclasses.

Light chains are called light chains because their molecular weight is less i.e. about 25,000. Molecular weight of heavy chains is 50,000 to 70,000 depending upon antibody isotype/class.

Basically, an antibody molecule has two functions i.e., antigen binding and effector functions. The binding of an antibody with an antigen is very specific (i.e., a single antibody can not bind with different antigens/epitopes) which is determined by the structural configuration of the antigen-binding region of that antibody.

Immunoglobulins have two Fab (“fragment, antigen-binding”) fragments and one Fc (“fragment, crystallizable) fragment.

Variable and Constant regions of Immunoglobulins

This antigen-binding region of an immunoglobulin is formed by the 100-110 amino acids located in the amino-terminal regions of corresponding heavy and light chains. These amino acids vary greatly among antibodies of different specificity. These segments of the variable sequence are called V regions: VL in light chains and VH in heavy chains.

Complementarity-determining regions (CDRs)

Within the variable regions of heavy chains and light chains, sequence variations are mostly concentrated in three discrete regions, known as hypervariable regions. Hypervariable regions form the antigen-binding site of the antibody molecule. As these regions are complementary to the structure of the epitope, they are also known as complementarity determining regions (CDRs)

Constant regions

The remainder of both the L and H chain contain regions of amino acid sequences which show very little variation among immunoglobulins and is called the constant region, CL on the light chain and CH on the heavy chain. Heavy chain constant regions are also the site for carbohydrate attachment.

This region of an immunoglobulin, known as Fc fragment, does not have antigen-binding activity but is involved in most of the effector functions.

Basic structure of an Immunoglobulin
Schematic diagram of Immunoglobulin

There are five basic sequence patterns that correspond to five different heavy-chain constants (C) regions γ, α, μ, ε, and δ. Each of these five different heavy chains is called an isotype. The heavy chains of a given antibody molecule determine the class of that antibody: IgG (γ), IgA (α), IgM (μ), IgE (ε), and IgD (δ).

Constant regions determine immunoglobulin class

Light chains have only one constant region whereas heavy chains have many constant regions CH1, CH2, CH3, and sometimes CH4. IgM and IgE have four heavy chain constant regions with approximately 440 amino acids but the remaining immunoglobulins (IgG, IgA, IgD) have only three heavy chain constant regions with approximately 330 amino acids.

Hinge regions

The γ, α, and δ heavy chains contain an extended proline-rich peptide sequence between the CH1 and CH2 domains known as the hinge region. Hinge regions give segmental flexibility to IgG, IgA, and IgD classes of antibodies as a result Fab can form different angles with each other while capturing the antigen. Although μ and ε heavy chains lack a hinge region, they have an additional domain of 110 amino acids that have hinge-like features.

Immunoglobulin classes

There are 5 classes of immunoglobulins IgG, IgA, IgM, IgE, and IgD as determined by the presence of unique amino acid sequences in the heavy chain constant regions. The basic structural properties of these immunoglobulin classes are discussed here briefly.

General structure of five major classes of immunoglobulins (antibodies)
General structure of five major classes of immunoglobulins (antibodies)
(Image source: Kubay Immunology)

Immunoglobulin G (IgG)

The IgG molecule consists of two γ heavy chains and two κ or two λ light chains. There are four human IgG subclasses, distinguished by differences in γ -chain sequence and numbered according to their decreasing average serum concentrations: IgG1, IgG2, IgG3, and IgG4. Find more about Immunoglobulin G (IgG) and its function here.

Immunoglobulin A (IgA)

The IgA molecule consists of two α heavy chains and two κ or two λ light chains.

The molecular formula of IgA is (α2κ2)n or (α2λ2)n, where n =1, 2, 3 or 4

IgA exists primarily as a monomer in serum but in external secretions, it (secretory IgA) is present as a dimer or tetramer linked by a J-chain polypeptide. Find more about immunoglobulin A and its function here.

Immunoglobulin M (IgM)

The IgM molecule consists of two μ heavy chains and two κ or two λ light chains. IgM has an “additional” heavy chain constant domain and the absence of a hinge region in the μ-chain.

The molecular formula of IgM is (μ2κ2)n or (μ2λ2)n, where n =1 or 5

IgM has two forms; monomeric IgM (membrane-bound on B cells) and pentameric IgM (secreted by plasma cells). In pentameric IgM, five monomer units are held together by disulfide bonds that link their carboxyl-terminal heavy chain domains (Cμ4/Cμ4) and their (Cμ3/Cμ3) domains held together by an Fc-linked polypeptide called the J (joining) chain. Find more about immunoglobulin M (IgM) and its functions here.

Immunoglobulin E (IgE)

The IgE molecule consists of two ε heavy chains and two κ or two λ light chains. IgE has an “additional” heavy chain constant domain and the absence of a hinge region in the ε-chain. Immunoglobulin E (IgE) is well known for its role in mediating immediate hypersensitivity reactions. More information about IgE will be published later in another blog post.

Immunoglobulin D (IgD)

The IgD molecule consists of two δ heavy chains and two κ or two λ light chains. IgD is typically coexpressed with IgM on the surface of mature B cells.

References and further readings

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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