Towards a better understanding of antigens

Comparing antigens and immunogens

An antigen is a substance, which binds to B-cell receptors (antibodies) or T-cell receptors. On the other hand, an immunogen is a substance that induces a specific immune response (either cellular or humoral or both). Although we use the word “antigen” more often than the word “immunogen” to denote a substance that induces a specific immune response, immunogen is most appropriate name for a substance that induces a specific immune response.

Immunogenicity and antigenicity

Immunogens and antigens may seem to have the same meaning, but a subtle difference exists between the two. Immunogens are substances that induce the formation of antibodies (in the case of a humoral response) or the expression of surface receptors on T-lymphocytes (in the case of cellular response) whereas antigens are substances that bind to antibodies and T-cell receptors. Moreover, all immunogens are antigens but few antigens are not immunogenic on their own.

Therefore, the definitive feature of an antigen is its ability to bind to the antigen-binding site of an antibody whereas that of an immunogen is the ability to induce a specific immune response.

Antigens may be contained within pathogens, may be expressed on surfaces of pathogens, or rather exist free in the atmosphere.

Most antigens are proteins; actually, proteins are the most potent immunogens. In addition, a number of immunogens are polysaccharides. Lipid immunogens are rather rare though they exist; lipid antigens exist as conjugate compounds with proteins (lipoproteins) or with polysaccharide (glycolipids).

Exogenous and endogenous antigens

It is very important to understand that some antigens (exogenous antigens) enter the body system from the environment whereas, some other antigens (endogenous antigens) form right inside our own body cells.

Endogenous antigens form right inside host cells when intracellular pathogens infect host cells. For instance, if a viral particle infects host cells, the infecting viral gene will encode for viral proteins and antigens. Viral DNA subverts host cells machinery making host cells to produce viral proteins. Same thing happens when other intracellular pathogen infects host cells. Thus, host cells infected with intracellular pathogens now encode for antigenic proteins.

Apart from endogenous antigens that develop form intracellular pathogens, host cells also produce endogenous antigens because of abnormal protein folding due to faulty gene, or error in translation. Moreover, host cells that have undergone gene mutation may encode for abnormal and aberrant proteins (antigens).

In either case, host cells generate abnormal self-proteins, which become target of immune attack.

Exogenous antigens invade the body from the environment. They may be inhaled, introduced through the skin, or ingested. Exogenous antigens are foreign antigens derived from the breakdown of extracellular pathogens.

Antigenic determinant also called epitope

Antigenic molecules, usually being large polymers of biological molecules, normally express a handful of surface features which act as specific sites of interaction for antibodies and T-cell receptors.

Moreover, within a certain antigenic molecule, only certain components of the molecule act as immunogen. In the case of a protein antigenic molecule, the actual immunogens could be a little more than one amino acid residue in the whole protein. In addition, BCRs (antibodies) or TCRs that the immune response generates recognize and bind these amino acid residues only and fails to bind other amino acid residues of the protein.

Therefore, we can say that an epitope is the part or component of an antigen that is the target of an immune response. It is possible that one antigenic molecule has one or more epitopes.

Antibodies or T-cell receptors formed against an immunogen bind only to the epitope that induced its formation.


Self-antigens are proteins expressed on the surface membrane of all body cells. A normal immune system recognizes self-antigens as part of host tissues and fails to react to them.

Foreign antigens are responsible for incompatibility during blood transfusion and rejection of tissue transplant. Typical examples are classes of proteins expressed on the surfaces of red blood cells; medical practitioners match these proteins (self-antigens) correctly to prevent incompatibility following blood transfusion. Incompatible matching causes an immune response against the received red blood cells.

T-independent antigens also called T-cell independent antigens

For a small number of antigens, their interaction at their antigen-binding site on B-cells surface receptors (immunoglobulin) is insufficient to activate and stimulate B-cells to produce antibodies. These antigens (T-independent antigens) bind and activate B-cells to produce antibodies directly without enlisting help from helper T-cells.

T-independent antigens are bacterial cell wall components (e.g. lipopolysaccharide) mainly, though lectins are also T-independent antigens.

The significance of T-cell help in B-cell response is evident by the fact that T-cell independent antigens are unable to trigger the formation of memory-cells. The implication is that a primary immune response occurs each time the individual encounters a cognate T-independent antigen. Moreover, the immune system produces IgM subtype (being the principal immunoglobulin secreted during every primary immune response); and lag time (being the time interval between exposure to antigen and detection of antigen-specific antibodies in the system) never reduces even after repeated exposure to the same antigen.

T-independent antigens induce antibody formation but are unable to induce immunological memory and only a minority of antigens is T-independent.

T-dependent antigens also called T-cell dependent antigens

The large majority of antigens are T-dependent; they must encounter their nearby helper T-cells in order to stimulate B-cells to produce antibodies. These antigens, called T-cell dependent antigens are soluble proteins mostly. T-dependent antigens induce both formation of antibody and formation memory B-cells (for immunological memory); therefore, B-cell response against a cognate T-cell dependent antigen is faster and more effective. This memory is because T-dependent antigens induce formation of memory B-cells.


Hapten is a Greek word for “fasten”. It denotes small organic molecules that are antigenic (i.e. can bind antibodies) but not immunogenic (being unable induce antibody formation). However, haptens are antigens because they bind specific antibodies though they are unable to induce antibody formation on their own.

However, if a hapten binds or attaches to an immunogenic protein (called carrier), the hapten-carrier complex induces the formation of specific antibodies against the hapten. Therefore, the body can generate antibodies against haptens if the haptens couple with an immunogenic protein.

Clinically, some drugs act as haptens and elicit allergic reactions when they complex to proteins in the human body. Examples are penicillin, streptomycin, sulpha- drugs aspirin etc. These drugs, by themselves, are not immunogenic and hence are unable to produce antibodies. Upon administration, the drug attaches to host proteins and forms drug-protein complexes. The drug is a hapten epitope whereas the protein is a carrier. Consequently, the body generates antibodies against the drug; the antibodies are IgE subtypes principally.

Hapten-containing drugs are most likely to elicit allergic reactions, whereas drugs that contain no haptens almost never elicit allergic reactions.

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