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.

References:

i) https://microbiologyinfo.com/antigen-properties-types-and-determinants-of-antigenicity/

ii) https://labweeks.com/antigens-determinants/

Determinants of antigenicity