Major histocompatibility complex (MHC) class II molecules function as communication platforms for the adaptive immune system. These molecules are specialized proteins that bind to fragments of extracellular pathogens and display them on the cell surface for recognition by specialized immune cells. This presentation of foreign material is a step in initiating a targeted immune response. Think of MHC class II molecules as a cellular display case, showing the immune system what potential threats have been found outside the body’s cells.
Structure and Location of MHC Class II
MHC class II molecules are glycoproteins found on the surface of specific immune cells. Structurally, they are heterodimers, composed of two different protein chains called the alpha (α) chain and the beta (β) chain. These two chains come together to form a specific three-dimensional structure that features a groove at the top. This peptide-binding groove is where a small fragment of an external protein, known as a peptide, is held for presentation.
The location of MHC class II molecules is highly specific. They are normally found only on the surface of professional antigen-presenting cells (APCs). The primary types of APCs are dendritic cells, macrophages, and B cells. These cells act as the sentinels of the immune system, constantly sampling their environment for signs of foreign invaders.
Dendritic cells are located in tissues throughout the body, where they can capture pathogens that breach the body’s initial barriers. Macrophages are large phagocytic cells that engulf and digest cellular debris, pathogens, and other foreign substances. B cells, while also producing antibodies, can internalize specific antigens through their B cell receptors and present them via MHC class II molecules.
The Antigen Presentation Pathway
The process begins when an antigen-presenting cell, such as a macrophage, encounters an extracellular pathogen like a bacterium. The APC engulfs the pathogen through a process called phagocytosis, enclosing it within a membranous sac called a phagosome.
Once inside the APC, the phagosome fuses with another vesicle called a lysosome. The resulting compartment, a phagolysosome, contains a potent mix of digestive enzymes and an acidic environment. Within this environment, the engulfed pathogen is broken down into numerous small peptide fragments.
Meanwhile, new MHC class II molecules are being synthesized in the cell’s endoplasmic reticulum and are transported through the Golgi apparatus. These MHC molecules are initially stabilized by a protein called the invariant chain, which also prevents them from binding to peptides prematurely. Vesicles containing these newly made MHC class II molecules eventually intersect and fuse with the phagolysosomes that hold the foreign peptides. Inside this combined compartment, the invariant chain is degraded, and a peptide from the digested pathogen is loaded into the groove.
With its cargo secured, the MHC class II-peptide complex is then transported to the surface of the antigen-presenting cell. Here, it is displayed outward, available for inspection by other cells of the immune system.
Interaction with Helper T Cells
The display of a peptide on an MHC class II molecule is a specific invitation for a particular type of immune cell. This interaction occurs with a class of lymphocytes known as Helper T cells, which are also identified by a surface protein called CD4. Each Helper T cell possesses a unique T-cell receptor (TCR) on its surface, which is capable of recognizing the specific shape formed by the combination of an MHC class II molecule and the peptide it carries.
This recognition event is highly precise, often compared to a lock and key mechanism. The T-cell receptor must be able to bind to both the MHC molecule and the specific peptide fragment being presented. A co-receptor on the T cell, CD4, also binds to a non-variable region of the MHC class II molecule, strengthening the connection and ensuring the correct cell types are interacting.
When a Helper T cell’s receptor successfully binds to the MHC class II-peptide complex, the T cell becomes activated. This binding event triggers a cascade of signals within the T cell, transforming it into an active participant in the immune defense. The activation bridges the initial detection of a pathogen by an APC to the mobilization of a full-scale adaptive immune response.
Role in Adaptive Immunity and Disease
Once activated, Helper T cells coordinate the adaptive immune response. They proliferate and differentiate into effector cells that release chemical messengers called cytokines. These cytokines act as instructions for other immune cells. For instance, some cytokines will enhance the pathogen-killing ability of macrophages, while others will stimulate B cells that have recognized the same pathogen to mature and produce large quantities of antibodies.
The antibodies produced by B cells are specifically tailored to the invader that was initially presented. These antibodies can then circulate throughout the body, neutralizing or marking the extracellular pathogens for destruction. This process is the foundation of immunological memory, allowing for a faster and stronger response upon subsequent exposure to the same pathogen.
This system, while effective, can sometimes malfunction. Autoimmune diseases can arise when the immune system mistakenly identifies the body’s own components as foreign. In conditions like rheumatoid arthritis or type 1 diabetes, MHC class II molecules may present “self-peptides”—fragments of the body’s own proteins—to Helper T cells. If these T cells become activated, they can orchestrate an immune attack against the body’s own tissues. In allergies, the system overreacts to harmless environmental substances, like pollen, presenting them as threats and initiating an unnecessary immune response. The fidelity of the MHC class II presentation system is therefore directly linked to maintaining a healthy balance between defense and self-tolerance.