An antigen is a molecule that can be recognized by the immune system. These molecules can originate from external sources, such as viruses or bacteria, or from the body’s own cells. The term “expression” in biology refers to the process where information from a gene is used to create a functional product, like a protein. Antigen expression specifically refers to a cell displaying these molecules, or fragments of them, on its outer surface.
This surface display is a communication method used by cells. By presenting antigens, a cell provides a snapshot of its internal state. This allows specialized immune cells to survey the body, assess the health of individual cells, and respond when necessary. The nature of the expressed antigen, whether it is a normal part of the body or a foreign substance, determines how the immune system will react.
The Biological Process of Antigen Expression
The expression of antigens on a cell’s surface is a regulated process. This mechanism relies on proteins known as the Major Histocompatibility Complex (MHC). These MHC proteins act as molecular platforms, binding to fragments of proteins from within the cell and carrying them to the cell membrane for display. The specific pathway used depends on where the original protein came from.
There are two primary pathways for this process, involving two different classes of MHC molecules. The MHC class I pathway deals with endogenous antigens, which are proteins made inside the cell itself. This includes normal cellular proteins and foreign proteins produced if the cell is infected by a virus or has undergone cancerous changes. Nearly all nucleated cells in the body express MHC class I molecules, offering a sample of their internal protein content.
The process begins in the cytoplasm, where proteasomes break down proteins into small fragments called peptides. These peptides are then transported into the endoplasmic reticulum, where they are loaded onto newly assembled MHC class I molecules. This structure is then transported to the cell surface, where the MHC-peptide complex is displayed for inspection by immune cells.
A different pathway, the MHC class II pathway, handles exogenous antigens, which are molecules that originate from outside the cell, such as bacteria. This pathway is used by specialized immune cells called antigen-presenting cells (APCs), including macrophages, dendritic cells, and B cells. These cells engulf external materials through endocytosis. Inside the cell, these foreign materials are broken down into peptide fragments by enzymes.
MHC class II molecules are synthesized in the endoplasmic reticulum and transported to these same compartments. A placeholder protein, the invariant chain, initially blocks the peptide-binding groove of the MHC class II molecule. In the endosome, this placeholder is removed, and the groove becomes available to bind with fragments of the exogenous antigen. The resulting MHC class II-peptide complex is then moved to the cell surface to be displayed.
Role in Immune System Recognition
Once an antigen is expressed on a cell’s surface, bound to an MHC molecule, it is surveyed by T-cells. Each T-cell has a unique T-cell receptor (TCR) on its surface, shaped to recognize a particular MHC-antigen combination. This interaction allows the immune system to distinguish between healthy cells, infected cells, and foreign invaders. The recognition process is highly specific, involving direct physical contact between the T-cell and the cell presenting the antigen.
The type of T-cell that responds is determined by the class of MHC molecule presenting the antigen. MHC class I-antigen complexes are recognized by CD8+ T-cells, often called cytotoxic T-cells. When a CD8+ T-cell’s receptor binds to an MHC class I complex displaying a foreign or abnormal peptide, it interprets this as a sign of cellular distress. This recognition activates the T-cell, prompting it to destroy the compromised cell directly.
MHC class II-antigen complexes are recognized by CD4+ T-cells, known as helper T-cells. When a CD4+ T-cell’s receptor connects with an antigen presented by an APC on an MHC class II molecule, it initiates a broader immune response. Activated helper T-cells release signaling molecules called cytokines. These signals coordinate and amplify the immune attack, activating other cells like B-cells to produce antibodies and directing cytotoxic T-cells to the site of infection.
A key feature of this system is its ability to differentiate “self” from “non-self.” During their development, T-cells that strongly react to the body’s own normal peptides are eliminated. This process of tolerance ensures that the immune system does not attack healthy tissues. When a T-cell encounters a normal “self” antigen being properly expressed, no immune response is triggered.
Antigen Expression in Disease
Alterations in the normal process of antigen expression are a feature of many diseases, allowing pathogens to evade detection or causing the immune system to malfunction.
Cancer
In cancer, tumor cells often manipulate antigen presentation to become invisible to the immune system. Some cancer cells achieve this by reducing or completely losing the expression of MHC class I molecules on their surface. This prevents them from displaying any internal peptides, including abnormal ones, effectively hiding them from patrolling CD8+ cytotoxic T-cells.
Cancer cells may also express antigens that are unique or are present at much higher levels than in normal cells. These are categorized as tumor-associated antigens (TAAs), which are normal proteins that are overexpressed, or as tumor-specific antigens (neoantigens), which are new proteins from mutations. These neoantigens are effective in stimulating an immune response because they are seen as completely foreign by T-cells. The presence and type of these antigens can vary between different cancers and patients.
Autoimmune Diseases
The immune system’s misinterpretation of antigen expression is a hallmark of autoimmune diseases. In these conditions, the mechanism of tolerance fails, and the immune system mistakenly identifies the body’s own healthy cells as foreign invaders. T-cells begin to recognize normal “self” peptides as if they were dangerous antigens. This leads to a sustained attack on healthy tissues and organs.
For instance, in type 1 diabetes, the immune system targets and destroys insulin-producing beta cells in the pancreas. In multiple sclerosis, the attack is directed against the myelin sheath that protects nerve fibers. In both cases, the cells under attack are functioning normally and expressing the expected “self” antigens. The pathology arises from an error in immune recognition, not an error in antigen expression.
Therapeutic and Diagnostic Applications
Understanding the mechanisms of antigen expression has led to the development of medical diagnostics and therapies. By targeting the specific antigens displayed on the surface of cells, clinicians can identify and combat diseases with greater precision. This approach is used in oncology, immunology, and infectious disease.
In diagnostics, the detection of specific surface antigens is a tool for identifying and classifying diseases. A technique called flow cytometry, for example, is used to diagnose blood cancers like leukemia and lymphoma. A patient’s blood or tissue sample is treated with antibodies engineered to bind to specific antigens on cancer cells. These antibodies are tagged with fluorescent markers, allowing a machine to count and sort the cells, providing a detailed profile of the cancer.
This knowledge has also advanced therapeutic strategies, such as CAR T-cell therapy, a form of cancer immunotherapy. In this treatment, a patient’s own T-cells are extracted and genetically modified to produce chimeric antigen receptors (CARs) on their surface. These engineered receptors are designed to recognize a specific antigen on the patient’s cancer cells. The modified T-cells are then infused back into the patient, where they seek out and destroy cells displaying that particular antigen.
The principles of antigen expression are also applied in vaccine development. Vaccines work by introducing a harmless version of a pathogen, or specific antigens from it, into the body. This allows antigen-presenting cells to process these foreign antigens and display them on their MHC class II molecules. This exposure trains the immune system, stimulating the production of memory T-cells and B-cells, so that if the body ever encounters the actual pathogen, it can mount a rapid and effective response.