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Allotype Antibodies: Definition & Immunology

Instructor: Vibha Jha

Vibha has doctorate in Immunology and has taught college level Microbiology

This lesson describes the meaning of allotype antibody. You will also learn how the allotypic differences between antibodies control the success of certain medical interventions.

Allotype Antibodies: Definition and Immunology

Before we understand the meaning of an allotype antibody, let us first review the general structure of an antibody. Antibodies are proteins made up of four chains - two light chains and two heavy chains. These proteins are essential members of our immune system and they are also known as immunoglobulins (Ig). As shown in Figure 1, both light and heavy chains are made up of variable and constant regions. The structure of the variable regions varies from one antibody to another antibody, whereas the molecular structure of the constant region remains same for one particular class of antibody.

Our body can produce a total of five different classes, or isotypes, of antibodies, namely, IgM, IgG, IgA, IgE and IgD. The constant regions on the heavy chain determine the class and sub-classes of antibodies. There are also two types of light chain, kappa and lambda. Each antibody will only have one type of heavy chain and one type of light chain. Structural differences in the constant region of either the heavy chain or light chain within a class of antibody is referred to as the allotype of an antibody.

Figure 1: The general structure of an antibody
Figure 1 illustrates the general structure of the antibody.

Why Do Allotypic Antibodies Exist?

Different versions of a gene within a species are known as alleles. For example, a gene that codes for hair color has various alleles, and therefore we have hair color ranging from black to blond. Similarly, there are various alleles that code for the constant region of an antibody. These alleles generate subtle amino acid differences resulting in structural variations in the constant region. Thus, individuals that have different alleles will have different allotypes of antibodies. Figure 2 shows the regions in the antibody that undergo structural changes to generate allotypic antibodies.

Figure 2: Sites of allotypic differences
Figure 2 shows the regions in the antibody structure that determine the allotypic differences of the antibodies

Naming an Allotypic Antibody

At present, at least 25 different allotypes of class IgG have been identified, and are noted Gm (for genetic marker). IgG has several subclasses, and the number between the letter G and m represents the subclass. Thus allotype 1 belonging to isotype IgG, subclass IgG1 is called G1m(1). The allotype for isotype IgA, subclass IgA2, is identified as A2m(1). The allotypes for kappa light chain are indicated km(1); there are no known allotypes for lambda light chain.

Immunological Significance of Allotypic Antibody

An individual carrying a certain allotype can generate antibody responses against an antibody of a different allotype, which may have significant immunological consequences. Let us find out what this means in the medical field. There are several diseases such as multiple sclerosis, rheumatoid arthritis, lupus, colorectal cancer, and others, where patients are treated with appropriate antibody therapy. These therapeutic antibodies (abbreviated for this lesson as TAb) are, most commonly, genetically engineered human proteins. Occasionally TAb cause adverse reactions or become ineffective. This powerlessness of TAb in most cases is due to the allotypic differences in the structures of the TAb and the antibody normally produced by the patient. Patient's immune system may recognize TAb as a foreign protein and start producing antibodies that neutralizes the effects of TAb.

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