Basic Structure and Classes of Immunoglobulin

In this article we will discuss about the basic structure and classes of immunoglobulin.

Antibodies are the specific glycoproteins (Immunoglobulin) produced by cells in response to stimulation by an antigen (Immunogen) and capable of reacting specifically with that antigen. Every immunoglobulin (in short they are written as Ig) has the same basic structure made up of four polypeptide chains (two heavy chains and two light chains).

These chains are held together by non-covalent forces and covalent disulphide bridges. Each chain has a variable part and a constant part of amino acids (Fig. 10.3). By splitting the immunoglobulin molecule using different enzymes it has been possible to learn the functions of the different parts of the molecule.

The enzyme, Papain splits the molecule into two Fab-fragments (Fab = fragment antigen binding) and one Fc-fragment (Fc = fragment crystallizable), while enzyme, Pepsin splits the molecule into one F(ab)₂ – fragment and several small and usually inactive peptides.

The differences in biological activities, together with distinct physico-chemical properties and different localizations have led to the division of antibodies into different classes and sub-classes.

The basic structure of Ig is illustrated below(Fig.10.3):

1. Basic Structure of Immuno­globulins:

A. Heavy and Light Chains:

All Igs have a four chain structure as their basic unit. One pair of the polypeptide chain contains approximately twice as many amino acids as the other pair. They are called heavy (H) chains (50-70 KDa.) and light (L) chains (25 KDa.) respectively.

B. Disulphide bonds:

1) Inter-Chain: The heavy chain and light chain and the two heavy chains are held together by inter-chain disulphide bonds.

2) Intra-Chain: Within each of the polypeptide chains, there are also intra-chain disulphide bonds.

C. Variable (V) and Constant (C) regions:

Both the H-chain and L-chain can be divided into two regions based on variability in the amino acid sequences.

1) Light Chain: Variable region, V_L (110 amino acids) and constant region, C_L (110 amino acids)

2) Heavy Chain: Variable region, V_H (110 amino acids) and constant region, C_H (330-440 amino acids).

The antibody (Ig) binds with the antigen through the V-region of the heavy and light chains, in other words a part of the Fab- fragment. The Fc – fragment is responsible for the biological activities.

D. Hinge region:

The region of which the arms of the antibody molecule forms a ‘Y’ is called the hinge region, because there is some flexibility in the molecule at this point.

E. Domains:

Ig molecule is folded into globular regions, each of which contains an intra-chain disulphide bond. These regions are called domains.

1) Light chain Domains – V_L and C_L

2) Heavy Chain Domains – V_H and C_H1 – C_H3(orC_H4)

F. Oligosaccharides:

Carbohydrates are attached to the C_H2 domain in most immunoglobulins.

Structure of the variable region:

A. Hypervariable regions (HVR) or Complementarity determining regions (CDR):

Comparison of the amino acid sequences of the variable regions of the Ig’s show that most of the variability resides in three regions (HVRI1, HVRI2, HVRI3) called the hypervariable region or the complementarity determining regions.

B. Frame work regions (FR):

The regions between the CDR’s in variable regions are called the frame work regions (FR1, FR2, FR3, FR4).

2. Immunoglobulin Classes and Sub-classes:

The Igs can be divided into five different classes in humans namely, IgA, IgD, IgE, IgG and IgM (Table 10.2). Among these IgA, IgD, IgE and IgG occur as monomers with the basic structure H₂L₂ i.e. two heavy and two light polypeptide chains. Serum IgA can polymerize to the dimeric (H₂L₂)₂ and the oligomeric (H₂L₂)_n forms.

IgA occurs mainly as a dimmer bound to a secretion component and to a polypeptide chain, the J-chain (J=join). IgM in serum occurs as pentamer (H2L2)S where the monomers are bound together by disulphide bridges and a J- chain. The classification of Igs is primarily based on the nature of H-chain and L-chain (Table 10.2).

The classes of Igs can be divided into sub­classes based on small differences in the amino acid sequences in the constant regions of the heavy chains. IgG is comprised of four sub­classes namely, IgGl (y-1 H-chain, 60-70% in serum), IgG2 (y-2 H-chain, 14-20% in serum), IgG3 (y-3 H-chain, 4-8% in serum) and IgG4 (y- 4 H-chain, 2-6% in serum). Among these IgG4 can bind to mast cells to accelerate allergic reaction in some cases.

IgA is comprised of two sub-classes namely IgAl (α-1 H-chain) and IgA2 (α-2 H-chain). IgE is involved in accelerating allergic reactions, though their concentration in serum is normally very low (0.001% of the total Igs). Elevated levels of IgE are found in the serum of patients suffering from allergic diseases. Certain cells like basophilic leukocytes and mast cells possess receptors for the Fc- fragment of IgE.