Antigenic determinants on immunoglobulins

  • Immunoglobulin molecules themselves function as potent immunogens when they are introduced into other animal species to induce an antibody response.
  • For studying the B cell development and humoral immune response, such anti-Ig antibodies are considered to be a powerful tool.
  • The antigenic determinants are also called epitopes on immunoglobulin molecules.
  • They are categorized into three major types. They are as follows:

 

A)Isotype

  • These determinants are common to or shared by all members of the same animal species (iso: same for each person).
  • They are constant-region determinants that collectively define each heavy chain class and sub class and each light chain type and subtype within a species.
  • A separate constant-region gene is responsible for encoding each isotype and the same collection of constant-region genes are carried by all the members of a species.

 

Image result for isotype antigenic determinants                 Image result for isotype antigenic determinants

 

  • Each normal individual will express all isotypes in the serum if it is within a species.
  • Different isotypes are expressed by different species as they have different constant-region genes.
  • For this reason, the antibodies from one species, when injected to other induce an antibody response as the isotypic determinants are considered as foreign by the antibody of other species.
  • Anti- isotype antibody is being used routinely for research purpose to determine the class or subclass of serum antibody produced during an immune response.
  • This may be also used to characterize the class of membrane-bound antibody present on B cells.
  • The isotypic markers on H chains distinguished the different H chain classes, i.e. H(α), H(δ), H(µ) and H( ɛ).
  • Isotypes (IgA, IgD, IgG, IgM, IgE) are determined by antibodies directed against the Fc portion of the molecule.

 

B)Allotype

  • Multiple alleles exist for some of the genes though all members of a species contain the same set of isotypic genes.
  • These alleles encode subtle amino acid differences which are called allotypic determinants.
  • These determinants occur in some but not in all members of a species.
  • Allotype is determined by the sum of the individual allotypic determinants that are displayed by an antibody.
  • Allotypes have been described in case of human for all four IgG subclasses, for one IgA subclass and for the κ light chain.

 

Image result for isotype antigenic determinants                                         Image result for isotype antigenic determinants

 

  • The gamma type allotypes are referred to as Gm markers.
  • About 25 different Gm allotypes have been identified which are designated by the class and subclass followed by the allele number.
  • G1m (1), G2m (23), G3m (11), G4m (4a) can be taken as example.
  • Only the IgA2 subclass has allotypes if we compare two subclasses of IgA i.e. A2m(1) and A2m(2).
  • There are three allotypes for κ light chain designated as κm(1), κm(2) and κm(3).
  • Each of these allotypic determinants indicates the differences in one to four amino acids that are encoded by different alleles of the same gene.
  • Antibody can be produced against the allotypic determinants by injecting antibodies from one member of the species to another member of the same species carrying different allotypic determinants.
  • Sometime mother during pregnancy also produces antibody to allotypic determinants in response to paternal allotypic determinants on the fetal immunoglobulins.
  • Antibodies can also be produced, during the blood transfusion, to the allotypic determinants.

 

C)Idiotype

  • VH and VL domains of a given antibody consist of unique amino acid sequence which works as antigen binding site.
  • But sometimes they also work as a set of antigenic determinants.
  • The sequence of a heavy- and light-chain variable regions lead to the arousal of idiotypic determinants.

 

Image result for isotype antigenic determinants                                     Image result for isotype antigenic determinants

 

  • Each individual antigenic determinant of the variable region is known as an idiotope.
  • Multiple idiotopes are presented by each antibody.
  • Among them, some of the idiotopes are the actual antigen- binding site and some comprising variable-region sequences outside of binding site.
  • The sum of the individual iditopes is called the idiotypic of the antibody.
  • If the antibodies are produced by the individual B cells derived from the same clone having identical variable-region sequences, idiotypes will be of same type.
  • Anti-idiotype antibody is produced by injecting the antibodies that have minimal variation in their isotypes and allotypes.
  • Due to the variation in isotypes and the allotypes, the idiotypic difference can be recognized.
  • Myeloma protein or monoclonal antibody is also used oftenly.
  • The formation of anti-idiotype antibody to the idiotypic determinants is resulted by the injection of myeloma proteins or monoclonal antibody into a recipient who is genetically identical to the donor.

Antigenic determinants on immunoglobulins

 

, , , , , , , , ,

About Shailesh Koirala

I am Shailesh Koirala
View all posts by Shailesh Koirala →

Leave a Reply

Your email address will not be published. Required fields are marked *