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:
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.Allotype:
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.
Idiotype:
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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