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Structure
of
Immunoglobulins
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There are five major types of antibodies or immunoglobulins, namely IgA, IgD, IgE, IgG and IgM which may differ in molecular weight in the range, of 150,000 to 720,000. Several of them can be further subdivided into subclasses like IgG1, IgG2, etc. Immunoglobulin G (lgG) is the commonest arid simplest of the immunoglobulins, which is a tetramer containing two identical high molecular weight or heavy chains and two identifical low molecular weight or light chains.
Each heavy chain is made up of about 500 amino acids, the light chain having only about half this number. These four chains are linked covalently by disulfide bonds in a Y -shaped structure.
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The Y shaped structure of antibody can be divided into following functional domains:
(i) antigen binding domains-Fv and Fab fragments and
(ii) effector domain-Fe fragment, which help in elimination of antigen.
Fv fragment is a heterodimer, consisting of the variable domains of the heavy chain and the light chain (YH and Yd. Fab fragment is also a heterodimer and consists of Fv fragment + CH1 and CL In other words, Fab consists of the entire light chain and the VH and CHI domains of heavy chain. Fc fragment consists of a homodimer with CH2 and CH3 domains of both heavy chains.
The entire antibody can be enzymatically cleaved at the hinge region into Fab and Fc fragments. The identification of these fragments of antibody has allowed the application of protein engineering and genetic manipulation for the production of novel antibodies without the use of hybridomas or animal cells (see next chapter for details).
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There are five types of heavy chains, designated as α (alpha), δ (delta), ε (epsilon), γ (gamma) and μ(mu) in IgA, IgD, IgE, IgG and IgM respectively. However, there are only two types of light chains, designated as κ (kappa) and λ (lambda). All five types of heavy chains occur in alternate forms containing either κ or λ chians, thus resulting in ten different combinations.
Each Ig chain consists of two distincts parts:
(a) C-terminal (carboxyl-terminal) constant part or C-region and
(b) N-terminal (amino terminal) variable part or V-region.
For each C-region (C α, C μ C γ, etc.), there can be several V sequences.
Separate sets of V sequences are known for heavy chains (VH) and light chains (V κ =for kappa and V λ = for lambda). The different V sequences have fair degree of homology only in some variable portions. There are distinct genes for the synthesis of- C and V regions of polypeptides.
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Immunoglobulin A (IgA) is the major antibody found in secretions (tears, mucus and saliva), which is the first defense against invading bacteria and viruses.
The functions of IgD and IgE are not known, although it is known that IgE differs from other immunoglobulins in being thermolabile, other immunoglobulins being stable at 50-60°C for half an hour to 4 hours. IgM, which appears early in response to many invading pathogens, is bigger than IgG (which replaces IgM later) and constitutes about 5-10% of the total immunoglobulins in the adult human, making about 125 +- 45 mg per 100 ml of serum.
Antibodies are also glycosylated, mostly carrying carbohydrate moieties in CH2 region. The, carbohydrate component of the immunoglobulin is an oligosaccharide with variable mono-saccharide units.
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It may include simple mannose rich units as in IgM or complex N- acetyllactosamine rich units as in IgG. In IgG, the carbohydrate portion is about 2.5% of the total molecule and it is equally divided between the two gamma heavy chains. It is linked through amino acids, aspartic acid and threonine residues in the polypeptide chain.
Mostly there is no glycosylation in Fab fragments and therefore glycosylation generally has no effect on antigen binding property of antibody. It, however, does influence effector function controlled by Fc fragment.
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