Antigen processing and presentation are fundamental biological processes that enable the immune system to recognize and respond to potential threats. This intricate communication system allows the body’s defenses to distinguish between healthy self-components and harmful invaders or abnormal cells. By breaking down and displaying molecular fragments, cells provide vital information that guides the adaptive immune response. This mechanism is central to how the immune system develops long-lasting immunity.
The Immune System’s Communication System
Antigens are molecular signatures identified by the immune system. They can be proteins, carbohydrates, lipids, or nucleic acids, originating from pathogens like bacteria and viruses, or from altered self-cells such as cancer cells. The immune system distinguishes between “self” antigens, which are usually tolerated, and “non-self” antigens, which trigger a response.
Antigens undergo “processing,” where they are broken down into smaller pieces called peptides. This degradation ensures that only specific, recognizable fragments are presented. Antigen processing enables the immune system to distinguish between self and non-self.
Following processing, “presentation” occurs, displaying these peptide fragments on the cell surface. These fragments are held within specialized Major Histocompatibility Complex (MHC) molecules, signaling to other immune cells, particularly T cells. This makes antigen processing and presentation an essential step for T cell activation.
Presenting Internal Threats
The Major Histocompatibility Complex (MHC) Class I pathway detects “internal” threats, such as virus-infected or cancerous cells. Nearly all nucleated cells, including muscle cells and keratinocytes, express MHC Class I molecules on their surface. This widespread expression allows the immune system to monitor the internal environment of almost every cell.
In this pathway, proteins produced inside the cell, including viral or abnormal proteins, are degraded. A cellular machinery called the proteasome breaks these proteins into small peptide fragments, typically 8-10 amino acids long. These peptides are then transported into the endoplasmic reticulum (ER) by a protein complex called Transporter Associated with Antigen Processing (TAP).
Inside the ER, these peptides bind to newly synthesized MHC Class I molecules, which are then transported to the cell surface. The presentation of these peptide-MHC Class I complexes signals to cytotoxic T cells (CD8+ T cells) that the cell is compromised. Upon recognition, CD8+ T cells activate and eliminate the infected or abnormal cell, preventing infection spread or tumor growth.
Presenting External Invaders
The Major Histocompatibility Complex (MHC) Class II pathway presents “external” threats, such as bacteria, toxins, or other pathogens encountered outside the cell. This pathway involves immune cells called Antigen-Presenting Cells (APCs). APCs include dendritic cells, macrophages, and B cells, strategically located to encounter foreign substances.
APCs engulf external pathogens through processes like phagocytosis or endocytosis into specialized compartments. Within these compartments, enzymes break down pathogens into peptide fragments, typically 13 to 25 amino acids long. Simultaneously, MHC Class II molecules are synthesized in the endoplasmic reticulum and transported to these compartments, initially bound to the invariant chain (Ii) to prevent premature peptide binding.
The invariant chain is then degraded, leaving a fragment called CLIP (Class II-associated Invariant Chain Peptide) in the MHC Class II binding groove. HLA-DM facilitates the exchange of CLIP for processed antigenic peptides. Once loaded with a specific peptide, the MHC Class II-peptide complex travels to the APC cell surface. This signals to helper T cells (CD4+ T cells), which then initiate a broader, more coordinated immune response against the external invader.
Immune Response and Beyond
Successful antigen processing and presentation activate the adaptive immune response. When T cells recognize their specific antigen presented by MHC molecules, they become activated, initiating immune events. This activation is crucial for both cell-mediated immunity, involving direct killing of infected cells, and humoral immunity, which leads to antibody production.
Antigen presentation is key to developing effective vaccines. Vaccines introduce specific antigens, which APCs process and present to T cells, enabling the immune system to recognize and respond to future pathogen encounters. This builds immunological memory, allowing a faster, more robust response upon re-exposure.
Understanding antigen processing and presentation is relevant to autoimmune diseases. In these conditions, the immune system mistakenly recognizes and attacks the body’s own “self” antigens. Genetic factors, particularly variations in MHC (HLA) genes, are associated with susceptibility to many autoimmune diseases, underscoring the precision required for proper immune function.