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In this article we will discuss about the classification of immunoglobulin.
1. Isotypes:
Based on the structure and sequence of their heavy-chain, constant regions, immunoglobulins are divided into five major groups called as classes which are again further subdivided into subclasses. In human, for example, there are five classes of immunoglobulins (commonly called GADME) viz., IgG, IgA, IgD, IgM and IgE. These classes not only differ in sequences but also in structure. All membrane of a species inherit and carry the same constant region genes.
Heavy-chain constant region (CH) structures which give rise to classes and subclasses are known as isotypic determinants. Isotypic determinants are constant-region determinants that collectively define each heavy-chain class and subclass and each light-chain type and subtype within a species (Table 4.6).
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Practical application of Iso-type:
Antibodies to isotypes are used for the quantitation of immunoglobulin classes and subclasses in various diseases.
2. Allotypes:
Allotypes are natural protein variants that are produced by the alleles of a gene. Through all members of a same species bear the same set of iso-type genes, multiple alleles exist for some of the genes. These alleles encode specific amino acid differences called as allotypic determinants, which are observed in some members of a species.
In human allotypes are studied for all four IgG subclasses, one IgA subclass and for k-light chain. The γ chain allotypes are known as Gm markers, e.g. G1m(1), G2m(23), G3m(11), G4m(4a). IgA subclass IgA2 are designated as A2m(1) and A2m(2). The k-light chain has three allotypes, designated km (1), km (2), and km (3). These three allelic variations are due to amino acid substitution at two sites 153 and 191 in the constant domain.
Practical application of Allotype:
1. Monitoring bone marrow grafts:
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Bone marrow grafts produce a different allotype in the recipient. These can be used to monitor the graft behaviour.
2. Forensic medicine:
Km and Gm allotypes are detectable in blood stains and semen specimens and are useful in forensic medicine.
3. Paternity testing:
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The immunoglobulin allotypes are one of the characteristics used in legal cases involving paternity determination.
3. Idiotypes:
The unique amino acid sequence of the VH and VL domains of a given antibody can function not only as an antigen-binding site but also as an antigenic determinant. The idiotypic determinants are generated by the conformation of the heavy- and light-chain variable regions. Each individual antigenic determinant of the variable region is referred to as an idiotope.
In some cases an idiotope may be the actual antigen binding-site, and in some cases an idiotope may comprise variable-region sequences outside of the antigen-binding site. Each antibody will present multiple idiotopes; the sum of the individual idiotopes is called the idiotype of the antibody.
Practical Applications of Idiotype:
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1. V region marker:
Id’s are a useful marker for a particular variable region.
2. Regulation of immune responses:
There is evidence that immune responses may be regulated by anti-Id-antibodies directed against our own Id’s.
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3. Vaccines:
In some cases anti-idiotypic antibodies actually stimulate B-cells to make antibody and thus they can be used as a vaccine. This approach is being tried to immunize against highly dangerous pathogens that cannot be safely used as a vaccine.
4. Treatment of B-cell tumours:
Anti-idiotypic antibodies, directed against an idiotype on malignant B-cells, can be used to kill the cells. Killing occurs because of complement fixation or because of toxic molecules bind to the antibodies.
