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What Are Antigens? An Overview

Antigens stimulate the body’s immune response when recognized by antibodies and activating lymphocytes. Immunologists can utilize the unique binding properties between antigens and antibodies to identify specific cell types, monitor cellular behavior, and isolate or separate target cells within a biological sample.

What Is an Antigen?

Antigens are molecules that trigger an immune response. They can come from many different sources and are not all inherently harmful or stemming from viruses or bacteria. Antigens can arise from common harmless substances or upon exposure to a pathogen capable of infection.

Antigens are small in mass and range in composition from proteins to lipids, polysaccharides, or other biomolecular substances. Antigen structure includes regions called “antigenic determinants” or epitopes that fit into a receptor or binding site. Antibodies use this site to recognize the antigen.

The strength of the antigen depends on the individual’s susceptibility to the foreign substance. This is primarily defined by the strength of the antigen-receptor interaction.

What Does an Antigen Do?

Antigens play a vital role in triggering the body’s immune response. Antigens fit into antigen-binding sites of antibodies or T- or B-cell receptors on the surface of lymphocytes circulating in the blood and tissues.

When the immune system identifies an antigen as foreign, an inflammatory response begins, activating immune cells to devise a specialized attack based on the structure of the recognized antigen. B and T cells produce antibodies and cytokines to quell the possibility of infection stemming from the antigen source.

B cells create and release antibodies, glycoprotein molecules that bind to antigens to render them harmless by neutralizing or triggering their engulfment by other immune cells. T cells that recognize foreign antigens can produce proinflammatory cytokines to tailor the immune response to the specific invader. In addition, some T cells can directly destroy antigen-carrying cells to stop an infection in its tracks.

Antigens play a vital role in triggering the body’s immune response. Antigens found on the surface of cells fit into antigen-binding sites on the paratopes of antibodies or T- or B-cell receptors on the surface of lymphocytes, such as CD3 in Pan T cells.

As pathogenic cells invade the body, the foreign antigens they present bind with free antibodies, the antibodies in B cell receptors, or antigen-binding sites on T cells. The antibody-antigen binding reaction may neutralize the antigen’s pathogenic properties or “flag” the pathogen with antibodies that other immune system elements can target.

Binding to a B cell receptor triggers the differentiation of the B cell into a plasma cell that produces antibodies corresponding to the foreign antigen and secretes cytokines that influence how other immune cells function. Binding to a T cell induces the T cell to differentiate into cells that can kill the pathogen or release cytokines to signal for a broader immune response.

The Importance of Antigens in Research and Medicine

Antigens are the foundation for understanding how the immune system identifies and combats pathogens. Researchers can uncover the mechanisms that trigger immune responses by studying antigens, paving the way for developing novel treatments and vaccines. This understanding helps scientists design targeted therapies to boost the immune systems’ ability to fight diseases. For example, research into tumor-specific antigens has led to breakthroughs in cancer immunotherapy for solid tumors, allowing for treatments that precisely target cancer cells without harming healthy tissue. The study of antigens also aids in the identification of biomarkers for various diseases, facilitating early detection and improving patient outcomes.

Antigens in Diagnostics

The application of antigens in diagnostics has revolutionized the ability to detect diseases accurately and efficiently. Diagnostic tests that utilize antigens, such as ELISA (enzyme-linked immunosorbent assay) and rapid antigen tests, are critical tools in identifying infections and other health conditions. These tests rely on the specific binding between antigens and antibodies to detect the presence of pathogens or disease markers in a sample. For instance, the development of rapid antigen tests for COVID-19 has been instrumental in managing the pandemic by enabling quick and widespread testing. Similarly, diagnostic tests for autoimmune diseases often measure the presence of autoantibodies against self-antigens, helping to diagnose conditions like rheumatoid arthritis and lupus.

Antigens in Therapeutics

Antigens are even at the heart of numerous therapeutic approaches, particularly in vaccination and immunotherapy. Vaccines use antigens derived from pathogens to stimulate the immune system, providing protection against diseases without causing illness. This principle has led to the eradicating of smallpox and significant reductions in diseases such as polio and measles. In cancer therapy, treatments such as CAR-T cell therapy involve engineering a patient’s T cells to express receptors that recognize and attack cancer-specific antigens, offering a powerful and personalized treatment option. Additionally, therapeutic antibodies designed to target specific antigens are used to treat various conditions, including cancers, autoimmune diseases, and chronic infections, showcasing the versatility and effectiveness of antigen-based therapies.

Types of Antigens

Multiple classifications exist for antigens based on their origin and recognition patterns. Self-antigens, or autoantigens, are produced in the body’s cells. Self-antigens are examples of endogenous antigens produced within the body; exogenous antigens are produced outside the body and are foreign to the immune system.

The immune system relies on antibodies or antigen receptors on T or B cells to bind with foreign antigens to detect, track, and destroy pathogens present in the body. Antigens can be any particle from any source, not only viruses or bacteria. Antigen types can also overlap, being defined as more than one type of antigen simultaneously.

Exogenous Antigens

Antigens that enter the body from the outside to infect or replicate are called exogenous antigens. The immune system gathers these antigens floating in the body to communicate what the potential threat looks like. The immune system sends out a signal—like a “wanted” poster—to the body and the antigen provides the “mugshot.”

Exogenous antigens activate the immune system into a tailored attack based on the recognized antigen. This activation triggers inflammation and the production of cytokines and antibodies to eliminate the threat. An example of an exogenous antigen would be allergens like pollen or dust.

Endogenous Antigens

Antigens generated inside the body from tissues or cells undergoing mutations are called endogenous antigens. These can arise due to changes in the body from viral infections causing transcription and translation errors or mutating proteins and nucleic acid sequences.

When the immune system recognizes these endogenous antigens, they cause inflammation and a targeted response. Cancer cells carry endogenous antigens that mark them as cancerous to the immune system, a crucial aspect of the body’s early cancer cell recognition and elimination.

Autoantigens

An autoantigen is not normally harmful but is misrecognized by the body as a threat or foreign pathogen, so the immune system launches an attack on its cells. Autoantigens drive autoimmune diseases, leading to tissue loss and cell damage from constant inflammation and an overburdened immune system.

B cells and T cells undergo a process called “central tolerance,” which is the result of “negative selection.” This process ensures that the body can distinguish harmless self-antigens from the threats posed by foreign antigens.

Antigen vs. Antibody

Antigens and antibodies are distinct and complementary biomolecules. Antibodies are proteins that function in the immune system to identify or neutralize hostile pathogens by binding to their antigens. The tips of Y-shaped antibodies feature specialized antigen-binding sites called paratopes, into which the epitopes of antigens fit like a key into a lock.

Pathogen vs. Antigen

“Pathogen” describes any bacterium, virus, parasite, or fungus that can cause infectious diseases. Pathogens often produce or present unique molecular structures that can act as an “antigen.” While antigens on the surface of native cells go unnoticed by the immune system, antigens produced by pathogens can trigger the body’s immune response.

Common Antigen Examples

Allergens

Allergens are exogenous antigens that cause immune responses in certain individuals. The threat an allergen poses to an individual depends on that individual’s tolerance and susceptibility to that particular allergen.

Common allergens include pollen, dust, some medications, animal dander, peanuts, and shellfish. Allergens cause allergic reactions, which are overreactions by the immune system to eradicate the allergen. These reactions can lead to sneezing, itching, and, in some cases, anaphylaxis.

Blood Group Antigens

Surface markers on red blood cells called blood group antigens determine an individual’s A, B, and O blood type. Each of the three types has a distinctly shaped antigen on the surface of the red blood cells. The presence or absence of Rh factor, another surface antigen, assigns whether a blood type is positive or negative. Discovering and understanding blood group antigens was integral to developing successful blood and organ transfusion technology. Obtaining a close match in blood type between patient and donor is crucial for transfusion success by reducing the likelihood that the patient’s body will recognize the transfused blood as foreign. Incompatible blood types can lead to extreme and life-threatening inflammation in the recipient.

HLAs

Human leukocyte antigens (HLAs) are a group of antigens present on all cells. They determine tissue compatibility for organ donors to reduce the risk of organ rejection. A close HLA match reduces the chance that the transplanted organ will cause an inflammatory response. Understanding HLAs was also crucial for the development of many transfusion-based treatments.

Vaccines

Vaccines are developed using what we know about the antigens on the surface of common viral and bacterial pathogens. They use weakened or inactivated antigens to stimulate an immune response that triggers antibody production. Upon re-exposure, the body can recognize the attack more quickly and already has the antibodies and T cells to fight the infection.

Antigens and Cell Sorting With Streptavidin Microbubbles for Negative Selection

Akadeum’s Microbubble kits utilize the antibody-antigen interaction to perform accurate and efficient cell separation protocols. The technology used in negative selection cell isolation kits involves mixing antibodies with a cell suspension and using microbubbles to gently remove unwanted cells from the sample population.

Researchers utilize the kit configured to enrich the cell subtype of interest to perform cell selection with our streptavidin microbubbles. This kit contains all necessary reagents, including streptavidin-coated microbubbles and a cocktail of biotinylated antibodies specific to the unwanted cell populations.

The biotinylated antibodies with paratopes corresponding to the epitopes on the unwanted cells are introduced to the sample. These antibodies bind to the antigens, identifying the target cells to be removed. Next, streptavidin-coated microbubbles are mixed into the sample. The streptavidin on the microbubbles binds to the biotin on the antibodies attached to the target cells’ antigens.

Finally, the buoyant microbubbles and their attached target cells gently rise to the sample’s surface to be removed, leaving the desired cells untouched and ready for analysis.

The selectivity of the antibody-antigen coupling, as well as the incomparable strength of the bonds between streptavidin and biotin in the streptavidin-biotin complex, make cell sorting with streptavidin microbubbles a compelling negative selection cell isolation method.

The biotinylated antibodies bind to only those cells in a sample that present the specific antigens with epitopes capable of binding to their paratopes. The unique binding correspondence between antibodies and antigens allows for precise labeling of only unwanted target cells, ignoring cell types that don’t feature these antigens. The strong binding affinity between biotin and streptavidin further ensures that these target cells remain securely adhered to the streptavidin-coated microbubbles as they float to the sample’s surface for collection and removal.

Advantages of Akadeum’s Microbubbles for Cell Separation

Traditional cell sorting, isolation, or separation methods—like fluorescence-activated cell sorting (FACS) or magnetic-activated cell sorting (MACS)—subject cells to intense mechanical or magnetic forces that can risk damaging the sample’s healthy cells. Moreover, these methods rely on expensive equipment requiring specialized training and may be especially cost- and time-prohibitive for small labs or research facilities.

Akadeum’s cell sorting kits with biotinylated antibodies and streptavidin microbubbles are affordable and easy to use. They utilize only the gentle mechanics of buoyancy to isolate cells, posing little risk to the viability of sample cells. Akadeum’s Microbubble kits are proven to deliver fast, scalable, and accurate results, yielding a pure sample of highly viable cells for analysis or downstream processing.

Learn more about Akadeum’s breakthrough microbubble methodology and the efficacy of our wide offering of products prepared for sorting a range of human cells. Use our precise antigen-antibody binding streptavidin microbubbles for high-accuracy cell separation. Check out our applications page to see how Akadeum’s microbubble technology is used worldwide.

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