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

Hi. In this video, we're going to be talking about MHC and antigen presentation. So MHC molecules are called major histocompatibility complex, and what they do is they bind to antigens and activate cells. Inactivated T cells, the things that express MHC, can be part of the innate immune system, part of the adaptive immune system. But, essentially, this is a major way that antigens are presented in order to activate them. Now there are two classes. This video is going to focus on class 1, and then the next one will focus on class 2. So class 1 is responsible for activating Tc cells. So remember these are cytotoxic T cells. And so, it has this structure, it consists of a single polypeptide chain, and this single chain is going to be attached to a peptide called a Beta 2 microglobulin. And, there is the combination of these two make a single peptide binding site that fits around an 8 to 10 amino acid peptide sequence on the antigen.

So here are the six steps to how it happens. First, you have a pathogen. This is going to be an intracellular pathogen. This is a big important part and a major differentiator between class 1 and class 2. So the intracellular pathogen is going to be present in the cytosol. So how did it get there? Well, the intracellular pathogen could be from a cell that's been infected and it's just already inside. It could be a cell that is maybe expressing viral genes that are just produced in the cell itself. But either way, there's an intracellular pathogen. This pathogen needs to be destroyed, so it's targeted via ubiquitin and passed through the proteasome for degradation. Remember the proteasome ubiquitin pathway that we talked about, so this is how it's destroyed, and this chops it into little pieces. Then these little antigens, these little pieces are transported into the ER. You don't need to know this, but there's a special complex that does this called the TAP complex. And then once it's in the ER, it binds to the MHC class 1 molecule. And then eventually, that's going to travel to the plasma membrane, be expressed, and then that antigen and MHC complex will activate the cytotoxic T cells. So here we have a pathogen, supposed to have an 'h' in it pathogen, and it is destroyed through the proteasome, then these little pieces travel into the ER where it complexes with MHC class 1. That then travels to the surface and activates Tc cells. So that is class 1, let's now turn the page.

Class II MHC

Okay. So in this video, we're going to be talking about the class 2 major histocompatibility complex or MHC, and this is responsible for binding to antigen and activating the T helper or the T regulatory cells. So, the structure for the class 2 is a little different. This consists of a heterodimer that is both encoded by MHC genes. These are 2 MHC genes that form a heterodimer. It also has a slightly longer peptide binding site than the class 2,12 to 20 amino acids, and this is going to bind the entire peptide. This is done by what I initially said as 6, but this is really 7 steps. So, the first step is we have an extracellular pathogen. This is a super important difference between the 2. This pathogen is going to be taken up by the cell. Then the pathogen, after it's taken up, moves to the lysosome for destruction. That's also a big difference. Then the pathogen is going to be degraded in the lysosome into tiny peptide fragments called antigens. Then, at the same time, the class 2 molecule is made in the ER and complexes with a small protein called CLIP. Then, this travels to the lysosome where the antigen is, is then cleaved to form CLIP, and then CLIP is eventually replaced by the antigen in the lysosome, and then the complex moves to the cell surface. So let's look at this example. We have a pathogen, it's extracellular, it is internalized, and it travels to the lysosome, where it is degraded into these small pieces. At the same time, you get the MHC class 2, which is made in the ER, and it's complexed with a protein, this blue protein here. This complex, attached to the protein, moves to the lysosome, where it is cleaved to form CLIP, and eventually replaced by the antigen. And then this will travel to the cell surface, where it activates T helper and T regulatory cells. So that is how class 2 works, which you see some major differences, including the extracellular pathogen, the lysosome destruction, the CLIP and the protein, and the type of cells that it activates. So with that, let's now turn the page.

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.