Functions and Structure: How MHC Class I and II Proteins Compare
MHC is nothing but a Major Histocompatibility Complex. These are a group of genes that code for proteins. These are found on the surface of the cells which help the body’s immune system recognize any foreign matter. It got this name since it was discovered during a study of tissue compatibility at the time of transplantation. Thus we can safely say that MHC checks upon the compatibility of the donor during the process of organ transplantation. It can also determine the chances of getting the autoimmune disease through cross-reacting immunization.
MHC proteins are present in all the higher vertebrates. MHC protein is of two types and they are:
MHC Class I
MHC Class II
MHC Class I
The MHC class I molecules are present in almost every nucleated cell in a living being. These are present in platelets as well but are absent in red blood cells that lack nuclei. The MHC class I protein helps in building cellular immunity. This immunity is necessary to take care of the pathogens that are capable of growing and reproducing inside the cells of their hosts. In 1989, the first structure of the MHC class I molecule was published named human HLA-A2. The main function of the class I MHC is to present the proteins that lie inside the cell to cytotoxic T cells which are also called ( CTLs ).
During the time of any infection, for example, consider a viral infection, the cell happens to release a foreign protein. At this time, as part of the MHC class I will exhibit these peptides on the cell surface. As a result, the CTLs that are specific for the MHC peptide complex will find and kill the presenting cells.
MHC Class II
Unlike MHC class I, the MHC class II molecules are confined to macrophages and lymphocytes which are the cells of the immune system. These are mainly found on dendritic cells, B cells, macrophages, etc.
When it comes to genes, each gene in our body has a large number of alleles. Alleles are nothing but the alternate form of genes that are capable of producing alternate forms of proteins. Therefore, we can easily conclude that it’s a very rare chance that any two individuals can have a similar set of MHC molecules. The MHC also contains a number of other genes that code for other proteins. These are called the class III MHC molecules.
During the early 1950s, when the skin graft experiments used to be carried out in mice, there were graft rejections. And these graft rejections were concluded saying that it was immune reactions by the host organism against the foreign matter or tissue. The MHC molecules on the cells of the graft tissue were recognized by the host as the foreign antigen. Therefore, for successful organ transplantation, it was necessary that the tissue type of the donor and the receiver should be similar to a large extent.
Difference Between MHC Class I and MHC Class II Proteins
FAQs on MHC Class I vs MHC Class II Proteins: Main Differences
1. What is the main difference between MHC Class I and MHC Class II molecules?
The main difference between MHC Class I and Class II molecules lies in their structure, the types of cells they are found on, the source of the antigens they present, and the type of T-cell they interact with. MHC Class I presents internal antigens to cytotoxic T-cells, while MHC Class II presents external antigens to helper T-cells.
2. What are the primary functions of MHC Class I and Class II proteins in the immune system?
The primary functions are distinct for each class:
- MHC Class I: Its function is to collect peptide fragments from proteins made within the cell (endogenous antigens), such as viral proteins, and present them on the cell surface. This presentation acts as a signal to CD8+ cytotoxic T-cells, which then destroy the infected or cancerous cell.
- MHC Class II: Its function is to present peptide fragments from pathogens that have been taken in from outside the cell (exogenous antigens) by professional Antigen-Presenting Cells (APCs). This presentation activates CD4+ helper T-cells, which then help orchestrate a broader immune response by activating B-cells and other immune cells.
3. On which types of cells are MHC Class I and MHC Class II molecules found, and why is this significant?
The distribution of MHC molecules is critical to their function:
- MHC Class I molecules are found on the surface of all nucleated somatic cells. This is significant because any cell can potentially become infected by a virus or become cancerous, and it must have a way to signal this internal problem to the immune system for elimination.
- MHC Class II molecules are found only on professional Antigen-Presenting Cells (APCs), like macrophages, dendritic cells, and B-cells. This restricted distribution is significant because it ensures that only specialised cells, whose job is to patrol for external threats, can activate helper T-cells and initiate a powerful, systemic immune response.
4. How does the antigen processing and presentation pathway differ for MHC Class I and Class II?
The pathways differ based on the origin of the antigen:
- MHC Class I (Endogenous Pathway): Proteins from within the cell (e.g., viral proteins) are broken down by the proteasome. These peptide fragments are then transported into the endoplasmic reticulum (ER), where they bind to newly synthesized MHC Class I molecules before being presented on the cell surface.
- MHC Class II (Exogenous Pathway): External pathogens are engulfed by an APC into a phagosome. This fuses with a lysosome, where the pathogen is broken down into peptides. Separately, MHC Class II molecules are produced in the ER and sent to this compartment, where they bind to the peptides and are then transported to the cell surface for presentation.
5. What are the key structural differences between MHC Class I and Class II molecules?
Structurally, MHC Class I and Class II molecules are distinct:
- An MHC Class I molecule consists of one long transmembrane chain (the α chain) and a smaller, separate protein called beta-2 microglobulin (β2m). The peptide-binding groove is formed by domains of the single α chain.
- An MHC Class II molecule is made of two transmembrane chains (an α chain and a β chain) that are roughly equal in size. The peptide-binding groove is formed by domains from both the α and β chains.
6. Why do MHC Class I molecules interact with CD8+ T-cells while MHC Class II interacts with CD4+ T-cells?
This specific interaction is due to molecular compatibility. The CD8 co-receptor on cytotoxic T-cells has a structure that specifically binds to a non-variable part of the MHC Class I molecule. Similarly, the CD4 co-receptor on helper T-cells binds specifically to a part of the MHC Class II molecule. This co-receptor binding acts as a crucial checkpoint, stabilising the interaction and ensuring that the correct type of T-cell responds to the specific threat being presented.
7. How do MHC molecules help the immune system distinguish between 'self' and 'non-self' proteins?
MHC molecules constantly present peptide fragments on the cell surface. In healthy cells, they present 'self' peptides from the cell's own normal proteins. During their development in the thymus, T-cells that react strongly to these self-peptides are eliminated. This process, called negative selection, creates self-tolerance. When a cell is infected or cancerous, its MHC molecules begin presenting 'non-self' peptides from the pathogen or tumour. Surviving T-cells recognise these non-self peptides as a danger signal, triggering an immune attack only against the compromised cells and leaving healthy cells unharmed.
