Antigen Definition, Function, and Types

An antigen is a molecule or particle, often found on the surface of cells, viruses, or bacteria, that triggers an immune response because the body recognizes it as foreign or non-self. The term “antigen” is a shortened term for ANTIbody GENerating substance.

Antigen Function

In immunology, antibodies and specific immune cells recognize antigens, leading to a targeted immune response. This response neutralizes or eliminates the foreign entity carrying the antigen, protecting the body from potential harm.

Examples of Antigens

Antigens take many forms. Typically, they are proteins, polypeptides, or sugars (polysaccharides) on the outside of cells or pathogens. Here are some examples of antigens:

• Bacterial cell wall components, such as lipopolysaccharides.
• Proteins on the surface of viruses.
• Pollen grains.
• Transplanted tissue or organ cells from another individual.
• Markers on blood cells and tumor cells (may be either “self” or “non-self”)

Antigen vs Antibody

While antigens are foreign substances that induce an immune response, antibodies are proteins produced by the immune system in response to these antigens. Antibodies specifically recognize and bind to their corresponding antigens, neutralizing them or marking them for destruction by immune cells.

B-Cells and T-Cells

The two types of white blood cells (lymphocytes) that respond to antigens are B-cells and T-cells. B-cells make antibodies. T-cells have antibody-like receptors on their surface that also bind antigens. T-cells serve a variety of functions, depending on the type of T-cell. Some directly attack and kill cells with antigens. Others signal for help in attacking invaders when they bind to an antigen. Still others reduce the activity of the immune system so that it does not attack healthy cells.

Both the antibodies made by B-cells and the T-cell receptor sites are specific. They only bind particular antigens. For example, an antibody that binds to pollen doesn’t bind to the flu virus.

Antigen Structure

Antigens are large, complex molecules that are often proteins or polysaccharides. They possess specific regions known as epitopes, which are the sites recognized and bound by antibodies. Each antigen has multiple epitopes, so several different antibodies recognize it.

An antibody or T-cell receptor has two binding sites per molecule. Antigens bind to receptors via a lock and key mechanism.

Antigen Properties

Antigens vary widely from one another, yet they share some common properties:

• Immunogenicity: An antigen has the ability to trigger an immune response. Age affects immunogenicity, so the very young and very old have a lower response to antigens.
• Composition: With a few exceptions, antigens are proteins, polypeptides, or sugars. Modern science has identified some inorganic (metal-based) molecules that induce an immune response.
• Size: Most antigens are large, with a mass of 14,000 to 6,000,000 Daltons.
• Specificity: The distinct structure of an antigen ensures it is recognized by a specific antibody.
• Tolerance: Normal cells have self-antigens. A healthy immune system tolerates self-antigens, ensuring it doesn’t attack the body’s own cells.
• Cross-reactivity: Some antigens react with antibodies produced against a different but related antigen. Many vaccines take advantage of this characteristic.

Antigen-Presenting Cells (APCs)

Antigen-presenting cells or APCs are immune cells that capture foreign pathogens, process their antigens, and present them on their surface using major histocompatibility complex (MHC) molecules. T-cells recognize this presentation, leading to their activation. Examples of APCs include dendritic cells, macrophages, and B cells.

How Antigens Work

When an antigen enters the body, the immune system responds:

1. Entry of the antigen into the body.
2. Recognition and uptake by APCs.
3. Processing and presentation of the antigen by APCs.
4. Activation of T cells by the presented antigen.
5. T cells stimulate B cells to produce antibodies specific to the antigen.
6. Antibodies bind to the antigen, marking them for destruction or neutralizing them.
7. Memory cells are formed to provide long-lasting immunity against the antigen.

Antigen Classification

There are two main methods of classifying antigens, based either on their origin or on the type of immune response they produce:

Based on Origin:

• Exogenous: Exogenous antigens come from outside the body, e.g., bacterial antigens.
• Endogenous: Cells within the body produce endogenous antigens, usually due to viral infections or mutations.
• Autoantigens: Autoantigens are the body’s own molecules that sometimes trigger an immune response, leading to autoimmune diseases. Tumor antigens are a type of autoantigen that identifies tumor cells.
• Neoantigens: Neoantigens are ones that are completely absent from the human genome. They offer promise for new cancer treatments because they are unaffected by T-cell tolerance.

Based on Immune Response:

• T-dependent antigens: T-dependent antigens require the presence of T cells to stimulate B cells to produce antibodies.
• T-independent antigens: T-independent antigens activate B cells directly.

Immunogens and Haptens

While immunogens and haptens relate to the concept of antigens, they differ in their inherent ability to provoke an immune response. Immunogens directly stimulate the immune system, while haptens require the assistance of a larger carrier molecule to do so.

Immunogens

An immunogen is a molecule or molecular complex that induces an immune response, leading to the production of antibodies or the activation of specific T cells. Essentially, all immunogens are antigens, but not all antigens are immunogens.

• Characteristics: Immunogens are typically large, complex molecules, often proteins or polysaccharides. Their size and complexity make it easy for the immune system to recognize them as foreign.
• Role in Immunity: The body recognizes immunogens as non-self, prompting the immune system to produce a specific response against them. This response involves the production of antibodies, the activation of specific T cells, or both.

Haptens

A hapten is a small molecule that, on its own, cannot induce an immune response. However, when a hapten attaches to a larger carrier molecule (usually a protein), it becomes immunogenic.

• Characteristics: Haptens are too small for the immune system to recognize when they are alone. They lack the necessary size and complexity to be directly immunogenic.
• Role in Immunity: When a hapten binds to a larger carrier molecule, the immune system recognizes the combined structure as foreign. The hapten-carrier complex then induces an immune response. Once this response has been established, the immune system recognizes and responds to the hapten alone, even without the carrier molecule.
• Examples: Common examples of haptens include certain drugs, dyes, and components of poison ivy. The allergic reactions some individuals experience to medications or chemicals are often a result of the immune system recognizing a hapten.

Antigen Tests

An antigen test is a diagnostic tool that detects the presence of specific antigens, which are typically parts of a pathogenic organism, within a sample. These tests help determine if an individual is currently infected with a particular pathogen.

How Antigen Tests Work

1. Sample Collection: A sample is usually collected from the body using a swab, often from the nasal or throat region, depending on the pathogen in question.
2. Binding: The collected sample gets mixed with a solution containing antibodies that have been engineered to bind specifically to the target antigen. Often, these antibodies are attached to a colored particle or another indicator.
3. Detection: If the target antigen is present in the sample, the antibodies bind to it. This binding event causes a visible reaction, such as a color change or the appearance of a line, which indicates a positive result.
4. Result Interpretation: The results are usually available within minutes. Most tests are visual, but some require a device to read the results.

Advantages and Limitations

• Advantages: Antigen tests offer rapid turnaround times and ease of use. They do not require complex laboratory equipment.
• Limitations: While they offer quick results, antigen tests are not as sensitive as other diagnostic methods, such as polymerase chain reaction (PCR) tests. This means they sometimes return a negative result even if the individual is infected, especially if the viral load is low.

Examples of Antigen Tests

1. Rapid Influenza Diagnostic Tests (RIDTs): These tests detect antigens associated with the influenza virus. They provide results in about 15 minutes and are popular in outpatient settings.
2. Rapid Strep Test: The rapid strep tests detects antigens produced by the bacterium Streptococcus pyogenes, which causes strep throat.
3. Respiratory Syncytial Virus (RSV) Test: This test identifies antigens associated with RSV, a common respiratory virus.
4. COVID-19 Antigen Tests: These tests detect specific proteins from the SARS-CoV-2 virus, which causes COVID-19. They are rapid tests to quickly screen individuals, especially in high-risk settings like healthcare facilities or events.

References

• Abbas, A.K.; Lichtman, A.; Pillai, S. (2018). “Antibodies and Antigens”. Cellular and Molecular Immunology (9th ed.). Philadelphia: Elsevier. ISBN 9780323523240.
• Lindenmann, J. (1984). “Origin of the terms ‘antibody’ and ‘antigen'”. Scandinavian Journal of Immunology. 19 (4): 281–285. doi:10.1111/j.1365-3083.1984.tb00931.x
• Parham, Peter. (2009). The Immune System (3rd ed.). Garland Science, Taylor and Francis Group, LLC.
• Wang, Q.; Douglass, J.; et al. (2019). “Direct Detection and Quantification of Neoantigens”. Cancer Immunology Research. 7 (11): 1748–1754. doi:10.1158/2326-6066.CIR-19-0107