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Antigenic Determinants on Immunoglobulins|Immune system|Immunity.

Posted by Mumtaz khan Friday, 9 March 2012

Antigenic Determinants on Immunoglobulins:
         Since antibodies are glycoproteins,they can themselves function as potent immunogens to induce an antibody response.Such anti-Ig antibodies are powerful tools for the study of B-cell development and humoral immune responses.The antigenic determinants,or epitopes,on immunoglobulin molecules fall into three major categories:isotypic,allotypic,and idiotypic determinants,which are located in characteristic portions of the molecule.
         Isotype determinants are consonant-region determinants that collectively define each heavy-chain class and sub class and each light-chain type and subtype within a species.Each isotype is encoded by a separate consonant region gene,and all members of a species carry the same consonant-region genes(which may include multiple alleles).Within a species,each normal individual will express all isotypes.Therefore,when an antibody from one species,each normal individual will express all isotypes in the serum.Different species inherit different constant-region genes and therefore express different isotypes.Therefore,when an antibody from one species is injected into another species,the isotypic determinants will be recognized as foriegn,inducing an antibody response to the isotypic determinants on the foriegn antibody.Anti-isotype antibody is routinely used for research purposes to determine the class or subclass of serum antibody produced during an immune response or to characterize the class of membrane-bound antibody present on B cells.
           Although all members of a species inherit the same set of isotype genes,multiple alleles exist for some of the genes.These alleles encode subtle amino acid differences,called allotypic determinants displayed by an antibody determines its allotypes.In humans,allotypes have been characterized for all IgG subclasses,for one IgA subclass,and for the light chain.The gamma chain allotypes are referred to as Gm markers.At least 25 different Gm allotypes have been identified;they are designated by the class and subclass followed by the allele number,for example,G1m(1),G2m(23),G3m(11),G4m(4a). Of the two IgA subclasses,only the IgA2 subclass has allotypes,as A2m(1) andA2m(2). The light chain has three allotypes.Each of these  allotypic determinants represents differences in one to four amino acids that are encoded by different alleles.
         The unique amino acid sequence of the Heavy and light domains of a given antibody can function not only as an antigen-binding site but also as a set of antigenic determinants.The idiotypic determinants arise from the sequence 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 maybe 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 idiotype of the antibody.
Because the antibodies produced by individual B cells derived from the clone have identical variable-region sequences,they all have the same idiotype.Anti-idiotype antibody is produced by injecting antibodies that have minimal variation in their isotypes and allotypes ,so that the idiotypic differences can be recognized.Often a homogenous antibody such as myeloma protein or monoclonal antibody is used.Injection of such an antibody into a recipient who is genetically identical to the donor will result in formation of anti-idiotype antibody to the idiotypic determinants.


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