What is the Difference Between Isotype Allotype and Idiotype

The key difference between isotype allotype and idiotype is based on the different antigenic determinants. While isotypes antigenic determinants characterize heavy chains based on classes and subclasses and light chains based on types and subtypes, allotype antigenic determinants relate to the allelic form of the immunoglobulin genes and idiotype is an immunoglobulin antigenic determinant present in the variable region of the antibodies.

Immunoglobulins play a major role in immune responses by specifically recognizing and binding to specific antigens. Antigens are proteins, which activates the immunity system. Isotype, allotype and idiotype are three types of antigenic determinants.

CONTENTS

1. Overview and Key Difference
2. What is Isotype  
3. What is Allotype  
4. What is Idiotype
5. Similarities – Isotype Allotype and Idiotype
6. Isotype vs Allotype vs Idiotype in Tabular Form
7. Summary – Isotype vs Allotype vs Idiotype

What is Isotype?

In mammals, antibodies or immunoglobulins are classified into main classes known as isotypes. Therefore, an isotype is a marker that corresponds to a particular antigen found in a specific class of immunoglobulins. It is a related protein or a gene from a particular gene family. There are five main classes of isotypes: IgA, IgD, IgE, IgG and IgM. They are classified based on the heavy chain they consist of. They are alpha, delta, epsilon, gamma, and mu, respectively. The expression of an isotype reflects the maturation stage of B cells. Naïve B cells express the antibody isotypes IgM and IgD with unmutated variable genes.

These are produced from initial transcripts, following alternate splicing. The expression of other antibody isotypes, IGA, IgE, and IgG, takes place after antigen exposure via a process of class switching. The enzyme activation-induced cytidine deaminase or AID induces the process of class switching. This process takes place after the B cell binds to an antigen through its B cell receptor.

IgG is the most common antibody isotype in normal human serum. Thus, it accounts for 70-85 % of the total immunoglobulin pool. IgM is the predominant antibody isotype in a primary immune response and accounts for about 5-10 % of the immunoglobulin pool. IgA exists as a monomer or a dimer and is the predominant antibody isotype in mucous secretions. It accounts for about 5-15 % of the immunoglobulin pool. IgD is present in large quantities on the membrane of B cells. It accounts for less than 1 % of the total plasma immunoglobulin. IgE is found on basophils and mast-cells in individuals and is associated with type 1 immediate hypersensitivity. IgE is found to be very scarce in the serum.

What is Allotype?

Allotype is also a type of variation in immunoglobulins that are found among antibody classes. Allelic variation is found between subtypes of antibodies. These polymorphic epitopes of immunoglobulins that differ between individuals are known as allotypes. These polymorphic epitopes are present on both heavy and light chains present on immunoglobulin constant regions.

Allotypes expressed on constant regions of heavy chain on IgG are denoted by Gm, which stands for a genetic marker. The allotypes expressed on IgA are denoted similarly as Am. In light chains such as kappa, it is denoted by Km. The exposure of an individual to a non-self-allotype can induce an anti-allotype response. But, not all variations in immunoglobulin amino acids sequence are responsible for immune responses. Antibody allotypes are used for therapies based on monoclonal antibodies.

What is Idiotype?

Idiotypes are immunoglobulin antigenic determinants present in the variable region of antibodies. These antigenic determinants are unique. They are present on the variable light region and variable heavy chain of individual antibodies. In other terms, idiotype is a shared property based on antigen-binding specificity between a group of T cell receptors or immunoglobulin.

The variable region of antigen receptors of immunoglobulins and T cells contain a specific amino acid sequence referred to as a complementary determining region. This particular amino acid sequence determines and defines the surface properties of the variable region. This determines the antigen specificity and thereby determines the idiotype of the molecule.

Several factors such as gene rearrangement, N-nucleotides, P-nucleotides, junctional diversity and somatic hyper-mutations, etc., determine antibody idiotype. Anti-idiotype is a form of idiotype that is present when one antibody binds to an idiotype of another antibody. These are important in drug therapeutics. Anti idiotypes based antibodies could be formed to bind specifically to one monoclonal antibody drug during such therapeutics.

What are the Similarities Between Isotype Allotype and Idiotype?

• Isotype, allotype, and idiotype are antigenic determinants.
• They relate to the immune system of the human body.
• All three types are present in different regions of an antibody.
• The activity of these antigenic determinants will induce the immune system when necessary.

What is the Difference Between Isotype Allotype and Idiotype?

Isotypes are antigenic determinants that characterize heavy chains based on classes and subclasses and light chains based on types, and subtypes, while allotype is an antigenic determinant specified by the allelic forms of the immunoglobulin genes and idiotypes are immunoglobulin antigenic determinants present in the variable region of the antibodies. So, this is the key difference between isotype allotype and idiotype.

The three types of antigenic determinants are present and observed in various instances. Isotypes are present in immunologically normal individuals. Allotypes are present during pregnancy and blood transfusion. Idiotypes are present during the transfusion of antibodies between genetically identical individuals.

Moreover, both isotype and allotype are localized in the constant region of the heavy chain and light chain but idiotype is present in the variable region of the heavy chain and light chain of the antibody.

The below infographic presents the differences between isotype allotype and idiotype in tabular form for side by side comparison.

Summary – Isotype vs Allotype vs Idiotype

Isotype, allotype, and idiotype are antigenic determinants that are present at different regions of an antibody. Both isotypes and allotypes are present in the constant region of the heavy chain and light chain, but idiotypes are present in the variable region of the heavy chain and light chain. All three types of antigenic determinants play an important role in the immunity system. Isotypes and idiotypes are important in detecting B cell tumours and treatment of B cell tumours, respectively. Allotypes play a major role in paternity testing and forensic sciences. Thus, this is the summary of the difference between isotype allotype and idiotype.

Reference:

1. “Allotypes.” Absolute Antibody, 17 July 2018.
2. “Antibody Isotypes & Subtypes.” Absolute Antibody, 17 July 2018.
3. Tankeshwar, Acharya. “Isotypes, Allotypes, and Idiotypes.” Microbe Online, 23 May 2021.

Image Courtesy:

1. “Mono-und-Polymere” By Martin Brändli (brandlee86) – Own work (CC BY-SA 2.5) via Commons Wikimedia
2. “AntibodyChains” By Original uploader was Yohan at fr.wikipedia, translated to English and converted to .svg by Sbmehta – based on a .png image here (CC BY-SA 3.0) via Commons Wikimedia