Difference Between MHC Class I and MHC Class II Proteins

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MHC Protein Types

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

                      MHC Class I

                        MHC Class II


These are present in all the cells which are nucleated including platelets and except red blood cells

Mainly found on B cells, dendritic cells, macrophages, and certain antigen-presenting cells only. 


The origin of the antigen that is presented by the MHC class I molecules is endogenous. 

The antigens that are presented by the MHC class II molecules come from an extracellular source


The enzymes that are responsible for generating peptides are cytosolic proteasomes. 

The enzymes that are responsible for generating peptides include lysosomal and endosomal proteases. 


Peptide loading takes place in the endoplasmic reticulum

Here peptide loading takes place in specialized vesicular compartments. 


The presence of many antigens lead to targeting cell for destruction

There will be the production of antibody due to the presence of foreign antigen


MHC class I molecules can be detected by the serology method

MHC class II molecules can be detected by serology as well as mixed lymphocyte reactions.

FAQ (Frequently Asked Questions)

1. What is the role of MHC class I protein?

Their main function is to expose the peptide fragments of the protein that lie within the cell to cytotoxic T cells. This leads to the response from the immune system against the non-self-antigen which is displayed with the help of MHC class I  protein.

2. What is the main role of MHC class II protein?

The main function of the MHC class II protein is to present the processed antigen that basically comes from the exogenous source to T-lymphocytes CD4(+). Thus, it causes the initiation of the immune response which is specific to the antigen.

3. Do B and T cells attack self-antigen?

The B and T cells are the white blood cells that recognize the antigen and are capable of differentiating between the ‘self’ with the ‘other’ antigens in the body. The B and T cells that recognize the ‘self’ antigen get destroyed even before they can mature thereby restricting the immune system of the body to attack its own cells.