Your immune system constantly scans for harmful invaders. How does it recognize them? Antigen acts as molecular fingerprints, allowing immune cells to distinguish between harmful and harmless substances. These molecules trigger responses that protect the body from infections and diseases.
This guide explains antigens, how they interact with immune cells, and how B cells and T cells detect and respond to them. You’ll also learn about antigen receptors, signaling pathways, and the balance between activation and suppression.
Antigen: Quick Summary
Do you just need the basics? Here’s a simple explanation of what is an antigen:
🟠 Antigens are molecules that cause an immune response. They can come from bacteria, viruses, toxins, or other non-living substances.
🟠 B-cell receptors (BCRs) recognize whole antigens in body fluids, while T-cell receptors (TCRs) detect antigen fragments on MHC molecules.
🟠 Antigen receptors have specific regions for binding antigens and signaling proteins that activate immune cells.
🟠 ITAM motifs in BCRs and TCRs help start immune signaling by bringing in tyrosine kinases like ZAP-70 and Syk.
🟠 Co-receptors like CD4/CD8 in T cells and CD19/CD21 in B cells make antigen receptor signaling stronger and more efficient.
🟠 ITIM motifs in inhibitory receptors recruit phosphatases such as SHP-1 and SHIP to slow down immune activation when needed.
🟠 The immune system controls activation and suppression to fight infections while avoiding attacks on healthy cells.
What Is an Antigen?
An antigen is any molecule that triggers an immune response. These molecules come from bacteria, viruses, fungi, or environmental sources like pollen and toxins. The immune system detects them using B-cell receptors (BCRs) and T-cell receptors (TCRs), which recognize specific molecular structures.
Some antigens originate from within the body, known as self-antigens. These normally do not trigger a response unless an autoimmune condition develops. Others come from outside sources, such as viruses or bacteria, and are classified as foreign antigens. A special type, called a hapten, is too small to cause a response alone but becomes immunogenic when attached to a larger protein.
B cells recognize complete antigens in body fluids, while T cells detect antigen fragments presented on major histocompatibility complex (MHC) molecules. This recognition ensures that the immune system can identify and respond to potential threats.
Antigens Processing and Presentation
For T cells to recognize an antigen, it must first be processed and displayed on the surface of another cell. This happens through antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells. These cells break down pathogens and present antigen fragments on major histocompatibility complex (MHC) molecules, which signal T cells to respond.
There are two main types of antigen presentation:
MHC Class I Presentation: Displays intracellular antigens (such as viral proteins) to CD8+ T cells, which then destroy infected cells.
MHC Class II Presentation: Presents extracellular antigens (such as bacterial fragments) to CD4+ T cells, which help coordinate the immune response.
This system ensures that T cells only activate when needed, preventing unnecessary immune responses. Without proper antigen presentation, T cells cannot detect hidden infections or abnormal cells, making this process essential for adaptive immunity.
How Antigen Receptors Work
Antigen receptors on B cells and T cells recognize harmful molecules and activate immune responses. These receptors allow immune cells to detect bacteria, viruses, and other threats. Each receptor consists of two parts: antigen-binding chains that determine what the cell recognizes and signaling proteins that start the immune reaction.
B-cell receptors (BCRs) attach to whole antigens in body fluids. When activated, B cells produce antibodies that neutralize pathogens. T-cell receptors (TCRs) recognize antigen fragments displayed by major histocompatibility complex (MHC) molecules on infected or abnormal cells. This allows T cells to either attack infected cells or coordinate other immune cells.
The structure of each receptor determines its function. BCRs are made of heavy and light chains, while TCRs consist of alpha and beta chains. Both types require accessory proteins to send signals into the cell.
| Feature | B-cell receptor (BCR) | T-cell receptor (TCR) |
| Antigen type | Free-floating molecules | MHC-bound fragments |
| Activation | Produces antibodies | Activates immune cells |
| Structure | Heavy and light chains | Alpha and beta chains |
Structure of Antigen Receptors
Antigen receptors on B cells and T cells recognize and bind to specific molecules, triggering immune responses. While both types share a similar purpose, their structures determine how they detect antigens and initiate signaling inside the cell.
B-Cell Receptor (BCR) Structure
B-cell receptors are immunoglobulin molecules composed of two heavy and two light chains. The variable regions of these chains determine what antigens the receptor binds to. Since the receptor’s cytoplasmic tail is too short to send signals, it relies on Igα and Igβ proteins to initiate activation.
Heavy and light chains form the antigen-binding site with high specificity.
Igα and Igβ contain immunoreceptor tyrosine-based activation motifs (ITAMs) that start signaling when an antigen binds.
Membrane-bound vs. secreted immunoglobulin: BCRs stay on the surface of immature B cells but become secreted antibodies after activation.
T-Cell Receptor (TCR) Structure
T-cell receptors consist of TCRα and TCRβ chains that detect antigen fragments displayed by major histocompatibility complex (MHC) molecules on other cells. Unlike BCRs, TCRs cannot bind free-floating antigens.
CD3 complex: Made up of CD3γ, CD3δ, and CD3ε proteins, which stabilize the receptor and help transmit signals.
ζ chains: Provide extra signaling capacity with multiple ITAM motifs.
Differences from BCR: TCRs always remain on the cell surface and require antigen presentation by MHC molecules to function.
How Antigen Receptors Trigger Signaling Pathways
When an antigen binds to its receptor on a B cell or T cell, a series of molecular events directs the immune response. These steps ensure a controlled reaction that activates the right pathways, allowing immune cells to detect and eliminate threats efficiently.
ITAM Motifs and Signal Initiation
Immunoreceptor tyrosine-based activation motifs (ITAMs) are specific sequences in antigen receptor complexes that start intracellular signaling. Each ITAM has two tyrosine residues that become phosphorylated by Src-family kinases when the receptor binds an antigen.
ITAM locations: Found in Igα/Igβ (B cells) and CD3/ζ chains (T cells).
Kinase activation: Fyn, Lyn, and Blk in B cells; Lck and Fyn in T cells.
Signal activation steps: Antigen binding → ITAM phosphorylation → Kinase recruitment → Signal amplification.
Signal Amplification Through Kinases
Once ITAMs are phosphorylated, they attract tyrosine kinases that amplify the signal and spread it through the cell. In T cells, the kinase ZAP-70 attaches to phosphorylated ITAMs in the CD3 and ζ chains, triggering further activation. In B cells, Syk binds to ITAMs in Igα and Igβ, setting off a similar process. These kinases activate additional proteins, such as LAT and SLP-76 in T cells and BLNK in B cells, which help extend the signaling cascade. This series of molecular events ensures that the immune response is strong and reaches the right cells to fight infections effectively.
Co-Receptors That Enhance Signaling
Co-receptors stabilize receptor interactions and increase kinase activity, making antigen detection more effective.
T cells: CD4 (MHC class II) and CD8 (MHC class I) bring Lck kinase closer to ITAMs, improving phosphorylation.
B cells: CD19/CD21 interact with complement-coated antigens to strengthen receptor activation.
Co-receptors help immune cells respond more quickly and effectively, ensuring that the immune system can recognize and react to foreign molecules with precision.
Regulation of Antigen Receptor Signaling
The immune system must regulate activation signals to prevent excessive or insufficient responses. While activation pathways amplify signals to fight infections, inhibitory mechanisms prevent overactivation that could lead to autoimmune diseases.
Inhibitory Signals and ITIM Motifs
Some immune receptors help slow down activation to keep the response in check. They do this by attracting phosphatases, which remove phosphate groups from signaling molecules, preventing an overreaction. One example is CTLA-4, which competes with CD28 for space on antigen-presenting cells, making it harder for T cells to stay active. FcγRIIB-1 lowers B-cell receptor signaling when it binds to antibodies, stopping unnecessary activation. PIR-B also helps by working with phosphatases to reduce immune cell activity. Inside immune cells, SHP-1 and SHP-2 turn off signaling pathways by removing phosphate groups from kinases. Meanwhile, SHIP changes membrane lipids to block further signals, ensuring the immune response shuts down when it’s no longer needed.
Balancing Activation and Suppression
The immune system constantly adjusts signaling strength to keep responses in check. If activation is too strong, it may cause autoimmune diseases, where the body mistakenly attacks its own cells. On the other hand, if suppression is too strong, the immune system becomes too weak to fight infections properly. Activators like ITAMs, ZAP-70, Syk, LAT, and BLNK help boost immune responses, while inhibitors such as ITIMs, SHP-1, SHIP, CTLA-4, and FcγRIIB-1 work to slow them down. This balance allows immune cells to react to harmful invaders without causing unnecessary damage to healthy tissues.
Memory and Adaptive Immunity
Once an infection is cleared, the immune system retains a memory of the antigen. Memory B cells and memory T cells remain in the body, ready to respond if the same pathogen is encountered again. This secondary response is faster and stronger than the first, often eliminating the invader before symptoms appear.
Memory B Cells: Quickly produce antibodies if the antigen reappears. These cells help provide long-term immunity after infections or vaccinations.
Memory T Cells: Rapidly recognize and kill infected cells or activate other immune cells. They persist for years, ensuring quick responses to familiar threats.
This adaptive feature of the immune system is why vaccines work. By exposing the body to a harmless form of an antigen, vaccines stimulate the creation of memory cells, allowing the immune system to respond rapidly to future infections.
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Antigen: Frequently Asked Questions
1. What is an antigen?
An antigen is any molecule that triggers an immune response, including proteins from viruses, bacteria, or toxins.
2. How do B-cell receptors (BCRs) recognize antigens?
B-cell receptors bind directly to free-floating antigens in body fluids.
3. How do T-cell receptors (TCRs) detect antigens?
T-cell receptors recognize antigen fragments displayed on MHC molecules by other cells.
4. What happens when an antigen binds to a receptor?
Binding activates signaling pathways that stimulate immune cells to respond.
5. What is the function of ITAM motifs in antigen receptors?
ITAM motifs initiate immune signaling by recruiting and activating tyrosine kinases.
6. How do co-receptors enhance antigen receptor signaling?
Co-receptors like CD4/CD8 in T cells and CD19/CD21 in B cells strengthen receptor activation.
7. What are ITIM motifs, and how do they regulate immune signaling?
ITIM motifs recruit phosphatases like SHP-1 and SHIP to suppress excessive activation.
8. Why does the immune system regulate antigen receptor signaling?
Regulation prevents harmful overactivation and ensures a balanced immune response.
Sources:
1. NIH
2. Britannica
3. Wikipedia
