To be an antigen, the molecule should have several characteristics:
Characteristic # 1. Foreignness:
The immune system possesses the capacity to distinguish between self and non-self. An antigen molecule must be recognised as non-self by the biologic system to elicit an immune response. When an antigen is introduced into an organism, the degree of its immunogenicity depends on the degree of its foreignness.
Generally, greater the phylogenic distance between two species, greater the structural (and therefore the antigenic) disparity between them. For example bovine serum albumin or BSA is not immunogenic to cow, but is strongly immunogenic to rabbit or chicken.
Characteristic # 2. Molecular Size:
The antigenicity of a substance bears a close relationship to its molecular size. The best immunogens or antigens tend to have a molecular mass approaching 100kD. Substances with molecular mass less than 5uD-10kD are poor immunogens (e.g., insulin with MW, 5,700). However, a few substances with molecular weight less than 1000 Da have proven to be immunogenic.
Characteristic # 3. Chemical Nature:
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Chemical composition of a substance largely affects its immunogenicity. Most naturally occurring antigens are proteins and some are polysaccharides. It is presumed that addition of aromatic amino acids, such as tyrosine or phenylalanine, profoundly enhances the immunogenicity of a substance.
For example, addition of tyrosine to a copolymer reduces the required minimum molecular weight from 30kD-40kD (without tyrosine) to 10kD- 20kD. In case of a protein antigen, all four organisations: primary, secondary, tertiary and quaternary contribute to the structural complexity of the molecule and hence affect its immunogenicity.
Characteristic # 4. Susceptibility to Tissue Enzymes:
It has been found that the substances which can be metabolised and degraded to soluble forms by the action of tissue enzymes, can act as good antigens. To generate immuno responses, antigens must be presented to TH cells in association with class II MHC molecules on an antigen-presenting cell and to Tc cells in association with class I MHC molecules on an altered self-cell.
Macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens. So before functioning as immunogens, substances must be degraded into smaller fragments of appropriate size containing the antigenic determinants within phagocytic cells or antigen-presenting cells.
Characteristic # 5. Spatial Arrangement:
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The spatial arrangements of different epitopes on a single protein molecule may influence the binding of antibodies in several ways. When determinants are well-separated, two or more antibody molecules can be bound to the same protein antigen without influencing each other. Such determinants are said to be non-overlapping.
When two epitopes are close to one another, the binding of antibody to the first epitope may cause steric interference with the binding of antibody to the second; such epitopes are said to be overlapping. In rare cases, binding of the first antibody may cause a conformational change in the structure of the antigen, influencing the binding of the second antibody by means other than steric hindrance. Such interactions are called allosteric effects.
Characteristic # 6. Species Specificity:
Tissues of all individuals belonging to the same species possess species specific antigens. Thus, human blood proteins can be differentiated from animal protein by specific antigen-antibody reaction.
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Characteristic # 7. Auto-Specificity:
The autologous or self-molecules are ordinarily not immunogenic, but, under certain circumstances, these may act as antigens. Lens protein and thyroglobulin may act as such auto-antigens.