Determinants of antigenicity

  • Antigenicity is the ability to combine specifically with the final products of the responses i.e. secreted antibodies and/or surface receptors on T cells.
  • All molecules having the property of immunogenicity also have the property of antigenicity but the reverse is not true.
  • Some small molecules are antigenic but they are not able to induce a specific immune response by themselves.
  • Such small molecules are called haptens.
  • These molecules lack immunogenicity and they can be made immunogenic by addition of large immunogenic protein called a carrier.
  • The whole antigen does not evoke immune response.
  • There are various small areas of chemical grouping on the antigen molecule which are called antigenic determinants.
  • They are also called epitope which determines specific immune response and reacts specifically with antibody.
  • Epitopes differ in specificity and potency.
  • Each determinant is about 25-34 A in size and 400-1000 M.W.
  • The antigenic property is lost by the denaturation of proteins.
  • The number of antigenic determinants of an antigen is referred to as its valency which can be of two types i.e. total and functional.
  • There are various determinants of antigenicity. They are as follows:

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A) Foreignness

  • The immune system has got the capacity of distinguishing between the self and non-self.
  • For eliciting an immune response, an antigen must be a foreign substance to the animal (non-self).
  • The flip side of the capacity to recognize non-self is tolerance of self, a specific unresponsiveness to self-antigens.
  • During the lymphocytes development, much of the ability to tolerate the self-antigens arises.
  • This occurs only when immature lymphocytes are exposed to self-components.
  • Cells are inactivated that are responsible in recognizing self-components during this process.
  • Antigens may be recognized as non-self, or foreign during the critical period by the immune system which have not been presented to immature lymphocytes.
  • The degree of immunogenicity determines the degree of foreignness.
  • The phylogenetic distance between two species if is greater, then the structural disparity between their constituent molecules will also be greater.
  • For example: Bovine serum albumin (BSA) is strongly immunogenic to rabbit but not in cow which is a common experimental antigen.
  • Similarly, BSA would be expected to show greater immunogenicity in a chicken than in goat, which is more closely related to bovines.
  • But, there are some exceptions to this rule as well.
  • Some macromolecules are present like collagen and cytochrome which have been highly conserved throughout the evolution.
  • For this reason, they express very little immunogenicity across diverse species line.
  • There are some self-components like corneal tissue and sperm which are effectively sequestered from the immune system.
  • But if these tissues are injected into the animal from which they originated, they will behave as an immunogens.

B) Macromolecular size

  • Molecular size is found to be closely related to the antigenicity.
  • Large molecules with high molecular size of 6.75 million Daltons like haemocyanin and other products like tetanus toxoid, egg albumin, thyroglobulin having molecular size of 14000-600000 Daltons are highly antigenic.
  • Substances having less molecular weight (insulin) than 10000 daltons are either non antigenic or weakly antigenic.

C) Chemical nature

  • Proteins and some polysaccharides are mainly naturally occurring antigens.
  • Proteins are more effective than polysaccharides in comparison to stimulate antibody production.
  • There are some exception for gelatin, histones and protamines which are non-antigenic due to their low tyrosine content (aromatic radical).
  • Presence of aromatic radical is essential for rigidity and antigenicity of a substance.


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D) Susceptibility to tissue enzymes

  • Tissue enzymes can convert some substances to soluble forms during metabolism which can act as good antigens.
  • Antigens introduced into the body are degraded by the digestive enzymes of the phagocytic cells.
  • Then they are broken down into smaller fragments of appropriate size which contains the antigenic determinants.
  • Substances that cannot be metabolized and converted to soluble forms are not antigens.

E) Antigenic specificity

  • Only some portions of the antigen show antigenic specificity with some specific active sites whereas the remaining portions are antigenically inert.
  • The determinant group is made up of six sugar residues that can act as antigenic determinant for polysaccharides molecules.
  • For protein molecules, it requires 5-7 amino acids residues and  five nucleotides are required for nucleic acid.
  • The antigens are multivalent and large antigens possess hundreds of different determinant groups.

F) Species specificity

  • Species specific antigens are present in tissues of all individuals in a particular species.
  • Thus, human blood proteins can be differentiated from the animal blood proteins by specific antigen-antibody reaction.

G) Iso-specificity

  • Allo-antigens or iso-antigens are found to be present in some members in a species but not in all the members.
  • They are able to produce iso-antibodies or alloantibodies.
  • Human blood is divided into various blood groups on the basis of human erythrocyte antigens and Rh antigens.
  • Histocompatibility antigens are present in the plasma membranes of tissue cells.

H) Organ specificity

  • Organs specific antigens are confined to a particular organ or tissue.
  • Certain proteins of brain, kidney, thyroglobulin and lens protein of one species share specificity with that of another species.

I) Autospecificity

  • The autologous or self-antigens are ordinarily not immunogenic.
  • But under certain circumstances lens protein, thyroglobulin and others may act as auto-antigens.
  • Some antigens like sequestered antigens are not recognized as self antigens.
  • Some antigens also develop later but remain absent in embryonic life are not recognized as self antigens.




Determinants of antigenicity