MHC and Antigen Presentation: Videos & Practice Problems

MHC (Major Histocompatibility Complex) molecules play a crucial role in immune response by presenting antigens to T cells. MHC Class I activates cytotoxic T cells by binding intracellular antigens processed via the proteasome, while MHC Class II activates T helper cells through extracellular antigens degraded in lysosomes. The structural differences include Class I's single polypeptide chain and Class II's heterodimer, with Class II binding longer peptide sequences. Understanding these mechanisms is essential for grasping adaptive immunity and therapeutic strategies in immunology.

Class I MHC

The major histocompatibility complex (MHC) plays a crucial role in the immune response by binding to antigens and activating T cells. MHC molecules are essential for antigen presentation, which is a key process in both the innate and adaptive immune systems. This summary focuses on MHC class I, which is specifically responsible for activating cytotoxic T cells (T_C cells).

MHC class I consists of a single polypeptide chain associated with a protein called beta-2 microglobulin. Together, they form a peptide binding site that accommodates an 8 to 10 amino acid sequence from an antigen. The process of antigen presentation via MHC class I involves several steps, particularly in the context of intracellular pathogens.

First, an intracellular pathogen, such as a virus, is present in the cytosol of an infected cell. This pathogen can originate from a cell that has been infected or from viral genes expressed within the cell. To eliminate the pathogen, it is tagged with ubiquitin and directed to the proteasome for degradation. This process, known as the ubiquitin-proteasome pathway, breaks down the pathogen into smaller peptide fragments.

Once degraded, these peptide fragments are transported into the endoplasmic reticulum (ER) through a specialized transport mechanism called the TAP complex. Inside the ER, the peptides bind to MHC class I molecules. After this binding occurs, the MHC class I-peptide complex is transported to the plasma membrane of the cell.

Finally, the MHC class I complex is expressed on the cell surface, where it can activate cytotoxic T cells. This activation is critical for the immune response, as it enables T_C cells to recognize and destroy infected cells, thereby playing a vital role in the body's defense against intracellular pathogens.

Class II MHC

The Class II Major Histocompatibility Complex (MHC) plays a crucial role in the immune response by binding to antigens and activating T helper and T regulatory cells. Unlike Class I MHC, Class II MHC consists of a heterodimer formed by two MHC genes, which creates a peptide binding site that is longer, accommodating peptides of approximately 12 to 20 amino acids. This allows for the binding of entire peptide fragments derived from extracellular pathogens.

The process of antigen presentation via Class II MHC involves several key steps. Initially, an extracellular pathogen is internalized by the antigen-presenting cell. This is a significant distinction from Class I MHC, which typically presents intracellular antigens. Once internalized, the pathogen is transported to the lysosome, where it undergoes degradation into smaller peptide fragments, known as antigens.

Simultaneously, the Class II MHC molecule is synthesized in the endoplasmic reticulum (ER) and associates with a small protein called invariant chain (Ii). This complex then travels to the lysosome, where the invariant chain is cleaved to produce a fragment known as CLIP. CLIP temporarily occupies the peptide binding site of the MHC Class II molecule until it is replaced by the antigenic peptide derived from the degraded pathogen.

Once the antigen is loaded onto the MHC Class II molecule, the complex is transported to the cell surface. This presentation is essential for the activation of T helper and T regulatory cells, which are critical for orchestrating the adaptive immune response. The entire process highlights the importance of extracellular pathogen processing, lysosomal degradation, and the unique role of Class II MHC in immune activation.

Which MHC class presents intracellular pathogens?

• A. MHC class I
• B. MHC class II

Answer: (A)

MHC class I is used to activate which of the following cell types?

• A. Antigen presenting cells
• B. Cytotoxic T cells
• C. Helper T cells
• D. Regulatory T cells

Answer: (B)

Here’s what students ask on this topic:

What is the difference between MHC Class I and MHC Class II molecules?

MHC Class I and MHC Class II molecules differ in several key aspects. MHC Class I molecules consist of a single polypeptide chain associated with β2-microglobulin and present intracellular antigens, typically from viruses, to cytotoxic T cells (Tc cells). These antigens are processed in the proteasome and transported to the endoplasmic reticulum (ER) via the TAP complex. In contrast, MHC Class II molecules are heterodimers composed of two polypeptide chains and present extracellular antigens to T helper cells (Th cells). These antigens are taken up by the cell, degraded in lysosomes, and then loaded onto MHC Class II molecules. The structural differences include Class I's single chain and Class II's heterodimer, with Class II binding longer peptide sequences (12-20 amino acids).

How do MHC Class I molecules present antigens to T cells?

MHC Class I molecules present antigens to cytotoxic T cells (Tc cells) through a multi-step process. First, intracellular pathogens, such as viruses, are degraded into small peptide fragments by the proteasome. These fragments are then transported into the endoplasmic reticulum (ER) by the TAP complex. In the ER, the peptides bind to MHC Class I molecules, which consist of a single polypeptide chain and β2-microglobulin. The MHC Class I-peptide complex is then transported to the cell surface, where it can be recognized by Tc cells. This recognition activates the Tc cells to destroy the infected cell, thereby eliminating the intracellular pathogen.

What role do MHC Class II molecules play in the immune response?

MHC Class II molecules play a crucial role in the immune response by presenting extracellular antigens to T helper cells (Th cells). These antigens are typically derived from pathogens that have been phagocytosed by antigen-presenting cells (APCs). Once inside the cell, the pathogen is degraded in lysosomes into peptide fragments. Simultaneously, MHC Class II molecules are synthesized in the endoplasmic reticulum (ER) and complexed with the invariant chain (Ii). This complex is transported to the lysosome, where the invariant chain is cleaved to form CLIP, which is then replaced by the antigenic peptide. The MHC Class II-peptide complex is then transported to the cell surface, where it can be recognized by Th cells, leading to their activation and subsequent immune response coordination.

What is the TAP complex and what is its function in antigen presentation?

The TAP (Transporter Associated with Antigen Processing) complex is a crucial component in the antigen presentation pathway of MHC Class I molecules. It is located in the membrane of the endoplasmic reticulum (ER) and is responsible for transporting peptide fragments generated by the proteasome from the cytosol into the ER. These peptides are typically 8-10 amino acids long and are derived from intracellular pathogens. Once inside the ER, these peptides bind to MHC Class I molecules, which are then transported to the cell surface to present the antigen to cytotoxic T cells (Tc cells). This process is essential for the immune system to recognize and eliminate infected cells.

How do MHC molecules contribute to adaptive immunity?

MHC molecules are essential for adaptive immunity as they present antigens to T cells, enabling the immune system to recognize and respond to pathogens. MHC Class I molecules present intracellular antigens to cytotoxic T cells (Tc cells), leading to the destruction of infected cells. MHC Class II molecules present extracellular antigens to T helper cells (Th cells), which then activate other immune cells, such as B cells and macrophages, to mount a coordinated immune response. This antigen presentation is crucial for the specificity and memory of the adaptive immune system, allowing it to effectively target and remember specific pathogens for faster responses upon re-exposure.