Immunogenetics class 1: different polypeptide chains of antibody

Different type of polypeptide chains of antibody and their coding gene segments.

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Studying mechanism, characteristic and different component of immune system is called as an immunology. Immunology is one of the challenging branch of biological science, and the genetics of immunology is even more tougher to understand.

Here we are discussing different gene segments which are involve in formation of different immunological proteins. So lets start from basic:

Any of the foreign particles which possibly harms our cell, are characterised as antigen and the protein which helps to destroy antigens are termed as antibody. Antibody is specialized antigen specific protein, each antibody is specific for a single type of antigen which means that for different types of antigen, antigen-specific different antibodies are synthesized by each  cell.

Structure of antibody polypeptide chains

Structurally, antibody is a Y shaped protein molecule which contains two light chain and two heavy chain (identical). Each light chain is made up of 220 amino acid, and each heavy chain is about 440-450 amino acid and, these chains are allied by disulphide bonds.

A variable region present on each heavy and light chain at N terminus end, makes it antigen specific. At the C terminus end, a constant region is present on both chains which is non variable and it gives structural support to antibody.

A constant region constructs effector functional domain, which is responsible for interaction of that antibody with other immune components. Depending upon the functionality of antibody, it is characterised into 5 major classes: IgM, IgD, IgG, IgE and IgA.

IgM and IgD are termed as surface antibodies which are embedded into cell membrane and every antigen is initially comes in contact with this surface antibody.

The light chain of antibody is of two type: kappa light chain and lambda light chain and, is determine by the constant region of light chain, now we can understand that though constant region is remain unchanged but plays important role in formation of each type of light chain.

The arrangement is hard to determine but it is easy to understand. Different DNA sequences for antibody (protein) light chain is located on different chromosomes. Rather to say gene it is called as gene sequences or gene segments because different sequences within the gene are allotted for formation of different polypeptides for variable region.

Different heavy chain, light chain, constant region and lambda and kappa chain polypeptides are synthesised by different gene segments. Now firstly we will discuss the arrangements of different gene segments for each chain.

Depending upon the function and location, two types of antibodies are present: The membrane bounded antibodies, present on the membrane of the cell and secreted antibodies, secreted from the B lymphocyte cell, induced by the antigen attack.

Light chain

Light chain is of two types kappa light chain or lambda light chain. Lets denote variable region as V, constant region as C and joining segments as J (joining segments are just a non coding intervening sequences). Keep in mind one point that each chain (whether it is light or heavy chain) is made up of long chain of polypeptides with N terminus and C terminus, it starts with N terminus at  variable region and ends at C- terminus towards constant region.

Number of gene segments for different type of polypeptide chains:

Kappa gene segmentsLambda gene segments Heavy chain
Variable region Vk=38Vλ 33VH=38-46
Joining region Jk=5Jλ =5JH=6
Diversity region 0

Constant region CK=1Cλ =4CH=9

Kappa light chain:

At the N terminus end the Vk gene segment is coding for 95 amino acid, Jk segment coding for 13 amino acids, and at C terminus end Ck gene coding sequences codes for remaining amino acid of light chain.

One chain of hydrophobic leader sequences are also present at N terminus end of kappa light chain which helps in transportation of antibody to the site of action. It is made up of 17-20 amino acids.

kappa chain synthesis.

During the development of B lymphocyte cells recombination of different Lk-Vk segment and Vk-Jk segments constructs different type of antigen specific antibody. The entire sequence of Lk-(Vk)Jk-non coding sequence-Ck is transcribed and the non coding sequences and other non functional sequences are removes from the mature kappa chain. Only Vk-Jk-Ck sequences are endure intact for development of particular antibody.

Lambda light chain

This gene segments are assembled during B lymphocyte maturation as well and creates different antibody though recombination of different gene segments. The maturation process is same as kappa chain but the segments are denoted as Jλ, Vλ, Cλ.

lambda chain gene segments.

Heavy chain

The genetic information for coding heavy chain gene segments are arranged on LH-VH, JH and CH gene segments. Here kappa or lambda variable region is remain same as light chain nevertheless one additional gene segment is present in heavy chain segment, a “diversity segment” or “D segment”.

mature heavy chain gene segment.

D segment awards additional diversity to antibody which is present on variable region of heavy chain. The D segment is made up of 2-13 amino acid long polypeptide chain. Here 4 separate CH gene segments are present for each Ig class heavy chain.

In humans, total 9 to 10 functional CH gene segments are present. The list of different segments are given into the table. In CH gene segments of heavy chain, the intervening sequences are typically psuedogenes ( sequences which are similar to functional gene but are non function), this psuedogenes are removed during maturation of B lymphocyte.

Depending upon the function and location, two types of antibodies are present: The membrane bounded antibodies, present on the membrane of the cell and secreted antibodies, secreted from the B lymphocyte cell, induced by the antigen attack.

Now the membrane bounded antibodies are fixed on cell membrane and embedded into lipid layer of membrane. The C terminus end of heavy chain of  antibody is hydrophobic in nature which helps them to fix in lipid layer, whereas the C terminus end of circulating antibodies are have hydrophilic end which makes them circulate freely.

IgM and IgD are fixed antibodies present on the surface of cell, others are freely circulated in body and depending upon the type of antigen, antibody is secreted.

Class switching

IgM and IgD are called as primary antibodies because both are present on the surface of cell, and are firstly interact with the antigen, secondary antibodies IgE, IgA and IgG are secreted depending upon the antigen present hence this class of antibodies are termed as secondary antibodies.

Now the antigen is recognised by the antibody, the cells are differentiated into mature B lymphocytes, instead of making one class of antibody, it makes another class of antibody. This phenomenon is called as antibody class switching.

The Constant segment of antibody decides which class of antibody will produce during the immune responds, here as the primary antibody is IgM, the CH gene segment is preliminarily same for all antibodies.

In class switching instead of producing IgM antibody, some mature B lymphocytes produces another class of antibody depending upon the gene segment arrangement of CH.

This antigen induced secondary antibody production and the mechanism is govern by rearrangement of different DNA segments of V,D,J and C regions followed by class switching recombination.

Which type of recombination induces class switching and how the gene arrangements occurs that we will discuss in the second segment of this article.

Read the next article of immunogenetics:

Immunogenetics class 2: antibody diversity

Story created by – Tushar Chauhan

written and reviewed by- Tushar Chauhan and Binal Tailor

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