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Major Histocompatibility Complex(MHC)

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  • Last Updated : 29 Nov, 2022
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The immune system is the most essential system of our body. It not only helps to protect the creature from foreign substances. Also, it helps to grow up without any outside disturbance. The immune system protects us from various threats. It protects from various foreign substances. It identifies them & destroys them. so, that the animal can able to grow up without any issues. Sometimes it is assumed that Immune System is only made with the White Blood Corpuscles. But that is not a correct assumption. It is a complete system where different components & proteins play an important role. Major Histocompatibility complexes (MHC) are similar kinds of a substance.

What is Major Histocompatibility Complex (MHC)?

Major Histocompatibility Complex (MHC) are the substances that are present on the surface of the nucleated cells. They are made with proteins. In the human body, there are nearly every cell has the Major Histocompatibility Complex (MHC) on its cell surface. Only, the Neurons don’t have such cells. As there is no nucleus present inside any neurons. The Major Histocompatibility Complex (MHC) is located inside the cells. But whenever there is a problem related to the Immune System of the body, it comes to the surface of the cell to do a task.

Major Histocompatibility Complex (MHC) identifies the foreign substances that are a potential threat to the body. There may be two types of foreign substances. One is linked with the body component & another is completely different from the body component. Word “Histo” means the tissues and the word “Compatibility” means living with harmony. A combination of these two words created Major Histocompatibility Complex (MHC).

Major Histocompatibility Complex (MHC) works with the T Lymphocytes. Major Histocompatibility Complex (MHC) only provides the signal of the foreign elements. The foreign element is going to be destroyed by the T lymphocytes. As per the type of the Major Histocompatibility Complex (MHC), the T lymphocytes also altered.

Discovery Of Major Histocompatibility Complex (MHC)

Major Histocompatibility Complex (MHC) was first discovered by the immunologist Peter Gorer in the 1930s. this was first discovered during the transplantation of the tissues. Peter Gorer was experimenting with the mice. He was trying to transplant tissues from one mouse to another mouse. Tissue transplantation is a process where a group of cells or tissue is injected or transplanted into another creature. Organ transplantation is the higher form of this experiment.

But during this experiment, Peter Gorer visualize something abnormal. He find out that, the mice on which the tissue was transplanted died some days. So, he decided to change the path of the experiment. He took a group of mice. And he makes a tissue transplant on both those groups. Both groups are different mice species. One group acts the same as the previous. One group eventually died. And another group survives.

After this experiment, he comes to the conclusion that there is something in the tissues that act as a foreign element for some mice. And for other mice, don’t have any such problems. Later, it is discovered that the substances that are destroying the mice are the MHCs. The MHCs also present in humans. That is why it is very crucial to check all the parameters before going for organ transplantation.

Types Of Major Histocompatibility Complex (MHC)

There are mainly two types of Major Histocompatibility Complex (MHC). As per the availability of the Major Histocompatibility Complex (MHC) on the surface of the cell & their function, the type of Major Histocompatibility Complex (MHC) are the followings:

  • Major Histocompatibility Complex (MHC) Class I: This is a type of MHC. These types of MHCs are only present on the normal cells’ surface. The cells have a nucleus. Mainly those cells have this type of MHCs.
  • Major Histocompatibility Complex (MHC) Class II: This is another type of MHC. These types of MHCs are only present on the surface of the immune system cells. They are not bothered about the nucleus in any cells. Mainly Dendritic Cell, B-Cells have those MHCs.
MHC Class I and MHC Class II


Major Histocompatibility Complex (MHC) Class I

  • MHC Class I is present in every nucleated cell except the nervous tissues & the platelets.
  • The size of the MHC Class I is 45 KD. These are the group of the major histocompatibility antigens
  • It was only able to work with Tc cells. These T lymphocytes help to destroy foreign elements.
  • It only works with the cell-mediated immune response. It only comes out to the surface whenever there is such a response.
  • It can able to bind with the CD-8 adhesion molecule of the T lymphocytes.
  • There are three types of HLA genes present inside a Major Histocompatibility Complex (MHC) Class I.
  • MHC Class I attaches to endogenous antigens.

Structure Of Major Histocompatibility Complex (MHC) Class I

The structure of the MHC Class I is completely simple. It is a chain-like structure. The whole structure is made up of a chain. It is similar to the RNA structure. The chain has one end inside the membrane of the cell. The other end makes the structure of the MHC Class I. There are mainly three folds on the structure. They all are made up of a bend of the chain.

There are two chains present. One is Alpha Chain & another is the Beta chain. Their chain is made up of the polypeptide molecule. There are three domains of alpha. They are Alpha1, Alpha2, Alpha3. There is only one domain of the Beta. The beta is completely detached from the cell membrane. The chain that is connected with the cell membrane, is made up of the domains of the Alpha.

Alpha chains are non-covalently attached to the Beta. Also, there are transmembrane glycoproteins on the alpha domains. They act as the HLA gene. There are two di-sulfate bonds in the Alpha2 & Beta domain. They help to make a tight bond there.

Major Histocompatibility Complex (MHC) Class II

  • These are the molecules that are present in the antigen-representing cells. This means those cells which are primarily responsible for destroying foreign substances.
  • It completely binds with the exogenous cells. This means those cells that completely come from the outside of the body
  • It only binds with the T Helper (Th) cells. This type of T lymphocyte can only recognize the response of the MHC Class II.
  • There is only one type of gene present inside the MHC class II. They are the simple HLA.
  • The size of the MHC Class II cells depends upon the chain type. As per the chain type, the size will get changed.
  • It can only able to get outside of the cell when the foreign element is inside the cell body.

Structure Of The Major Histocompatibility Complex (MHC) Class II

There are mainly two types of chains. There is an Alpha & Beta chain. But the structure is different from the structure of Class I. Here, two chains are anchored inside the cell membrane. Both chains have one side inside of the cell membrane. The other side makes the structure. There are two different changes. And those chains make different domains.

The Alpha chain will create two domains. They are the Alpha1 & Alpha2. The Beta chain will also make two different domains. One is Beta1 & another is Beta2. All the chains will attach by non-covalent bonds. There are di-sulfate bonds in the domain. Except for the Alpha2 domain, in every domain, there is the di-sulfate bond. This bond will help to hold the domain to its structure. The Alpha1 & Beta1 will jointly make the peptide bonding place. This is the place where the foreign substance will get attached. As a result, the signal will go to the T Helper cells to destroy the substances.

Antigens Presentation

Antigen Presentation


There is mainly one type of antigen present in the Major Histocompatibility Complex (MHC). They are the Human Leukocyte Antigen (HLA). This is the main driving force of the Major Histocompatibility Complex (MHC). There are many types of HLA. In the MHC Class I, there are three types of HLAs. They are HLA -A, HLA -B & HLA -C. In the MHC Class II, there are also three types of HLAs. They are HLA -DR, HLA -DQ & HLA -DP.

The HLA helps to identify foreign elements. There are all types of cells inside the body. As MHC Class I is only present over the nucleated cells. So, there should be a recognition mechanism to find out the proper substance. The HLA does the same thing. It was first able to recognize the foreign element type. If the elopement is derived from the body, the proper HLA provides the signal to MHC Class I. If the element is not derived from the body, then the HLA provides the signal to the MHC Class II. Then they start their usual work there.

Importance of Major Histocompatibility Complex 

Major Histocompatibility Complex (MHC) is an important substance in our body. It helps to recognize the potential threat to our immune system. If a foreign object enters the body, it is a necessary task to destroy it. But it is not only possible by the WBCs. Some substances are related to our body’s important processes. Those things need to be kept as it is. So, there needs to be a difference between the essential substance & foreign object. Major Histocompatibility Complex (MHC) plays that role.

Depending upon the case, the MHCs can able to react in a different format. They are not the antibody. They are not directly acting upon the foreign elements. They can able to recognize the element. After that, they send one special message to the T lymphocyte cells. These cells will responsible to destroy the elements. The job of the MHCs is only to send a proper message to the T cells. These cells will then act upon those cells. Sometimes the cell needs to be dead to save the other cells. Or sometimes only the foreign element will get destroys.

If the MHCs are not present in the body, it will be difficult to recognize the foreign elements. As a result, those elements will not destroy. That can able to create a severe problem for the body. Also, some elements are helpful for our bodies. If those substances are removed from our bodies, there will be more reactions in the body. So, the MHCs are the most important message sender to the foreign element destroyers.

Functions Of Major Histocompatibility Complex (MHC)

  • The main function of the Major Histocompatibility Complex (MHC) is to help the immune system. T Lymphocytes don’t have the ability to recognize the potential threat to the body. MHCs mainly recognize the threat to the body & hence provide a signal to destroy them.
  • Major Histocompatibility Complex (MHC) guides the T Lymphocytes cell to destroy the foreign element inside of the body. As per the category of the foreign element, it binds to the element. After that, it sends a signal to the T Lymphocyte cell to destroy it. And eventually, it gets destroyed.
  • MHC molecules often bind with the peptide epitopes. This causes the ligands for the TCRs. This ligand will again help in the reallocation of the tissues. This is also can be done with the T cells. After the decomposition of the cell, the ligands help to restore the structure of the cell to its previous form.

FAQs on Major Histocompatibility Complex

Question 1: Who invented the MHCs & when?


Scientist Peter Gorer invented the MHCs in 1930. He made an experiment on mice. As a result, he got a set of MHCs. Later scientists discovered that the MHCs are present inside the body of every higher vertebrate.

Question 2: What is HLA?


The full form of HLA is Human Leukocyte Antigen. They act as a special gene in MHCs. As the HLA is present inside of the MHCs. Sometimes the MHCs are also referred to as the HLA. So, the HLA & the MHC can define the same object.

Question 3: What is the size of peptides of the Alpha chain & Beta chain of the MHC Class II?


The size of the peptides in the Alpha chain is 33KD. And the size of the peptides of the Beta chain is 28 KD. As these two chains are different from each other. The peptide size of the chains is also different.

Question 4: Where is the peptide binding cleft of MHC Class II?


Peptide binding cleft is present in the MHC Class II. The Alpha1 & Beta1 domain in the MHC Class II will make this peptide binding cleft. This cleft is used for the binding of foreign elements to provide a signal to the T lymphocytes.

Question 5: Do neurons have MHCs?


No. Neurons don’t have the MHCs. Only those cells that have the nucleus can only have the MHCs. Only the MHC Class II doesn’t depend on the presence of the nucleus. But they are available only on specific cells. So, there are no MHCs inside the neurons.

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