What are the Factors That Influence Immunogenicity of an Antigen?



Factors that generally influence Immunogenicity of an antigen are as follows:

1. Chemical Composition and Heterogeneity:

Chemical composition and heterogenity of antigens play an important role in immunogenicity. Generally proteins are good immunogens because of their high internal molecular complexity and heterogeneity.

A homopolymer polypeptide chain of any amino acid, even though big in size, fails to induce immune response due to lack of heterogeneity. Addition of different amino acids at different sites of the same homopolymer makes it immunogenic.

Since the structural complexity of a protein is different at different levels of formation, the immunogenicity of a protein during its formation and after its formation are different.

Study of synthetic lysine and glutamic acid co-polymers suggest that a minimum of substance with 30000-40000 Daltons molecular weight is required to be immunogenic, but when tyrosine is added to this synthetic co-polymer, a molecule of even 10000- 20000 Daltons molecular weight is sufficient to be immunogenic.

The increased complexity of the co-polymers by the addition of other amino acids helps to raise its immunogenicity.

2. Size

Generally the size of the antigen molecule influences the immunogenicity. Substances with a molecular weight of about 100000 Daltons show best immunogenicity and substances less than 5000 to 10000 Daltons are poor immunogens.

For example large molecules such as hemocyanin (6000.000 dt) and thyroglobulin (9669000 dt) show excellent immunogenicity. The proteins like insulin, histone etc. with low molecular weight fails to produce proper immunological response when exposed to immune system.

3. Foreignness

The very important and essential character required, for any substance to be immunogenic is its foreignness.

Since immune system is designed to react with foreign molecules, antigens from related species are less antigenic than that of unrelated species.

The phylogenetic distance between two species generates disparity between antigens, but there is same exception to contain molecules such as collagen, and cytochrome C, because they are highly conserved throughout evolution and therefore display very little immunogenicity across diverse species lines

4. Susceptibility to Antigen Processing and Presentation

Antigen presentation to TH cells through antigen presenting cells after processing is essential for both humoral and cell mediated immune responses. Hence molecules that cannot be processed and presented to the T cells become poor immunogens.

In this aspect, large insoluble molecules are more immunogenic than smaller ones because larger molecules are easily identified and phagocytosed by antigen presenting cells for processing and presentation.

5. Degradability and Solubility

The substance that is not soluble in body fluids fails to induce immune response. If the substance is soluble in body fluids there is a possibility of exposure of hidden epitopes to induce immune response. For example pneumococcal polysaccharides are greater immunogens in mice but not in rabbits, because the pneumococal molecules are highly soluble in mice body fluids but not in rabbits.