Anatomy & Organs

Major Histocompatibility Complex – Structure, Function & Diseases

Major histocompatibility complex

The major histocompatibility complex is a complex of genes that produce immune proteins. These proteins are responsible for immune recognition and immunological individuality. They also play a major role in tissue compatibility in organ transplants .

What is the Major Histocompatibility Complex?

Major histocompatibility complexes are formed in all vertebrates. They are responsible for the immune system and the recognition of the body’s own proteins. Thus, as part of the major histocompatibility complexes , antigens are presented on the surface of all cells .

All nucleated cells contain receptors for the MHC class I protein complexes. The MHC class II protein complexes are in turn presented by the so-called antigen-presenting cells such as macrophages , monocytes , dendritic cells in the thymus , lymph nodes , spleen and blood , or by B lymphocytes. The difference between both major histocompatibility complexes is that intracellular antigens are presented in the MHC class I protein complex and extracellular antigens in the MHC class II complex.

There is a third major histocompatibility complex called the MHC class III protein complex. This third complex is made up of plasma proteins that cause a non-specific immune response. All three complexes regulate the immune system and at the same time ensure tolerance to the body’s own proteins. Foreign proteins originating, for example, from viruses or from degenerated cells are identified via the MHC class I protein complex . The infected or degenerated cell is destroyed by killer T cells. In the case of the MHC class II protein complex, the presence of extracellular foreign protein activates the T helper cells, which are responsible for the formation of antibodies .

Anatomy & Structure

Both major histocompatibility complexes consist of protein complexes that bind smaller peptides that form from cleavage of proteins, either self or non-self. The MHC class I protein complex is a complex of a heavy unit and a smaller unit (β2-microglobulin) that have bound the antigen.

For this purpose, the heavy chain contains three domains (α1 to α3), while the β2-microglobulin represents the fourth domain. Domain α1 and α2 form a cavity in which the peptide is bound. The peptides are formed in large numbers from the constantly synthesized proteins by the enzyme proteasome. The cytotoxic T-cells recognize whether they are degradation products of endogenous or exogenous proteins. If the proteins come from viruses or abnormal cells, the killer T cells immediately begin to destroy the corresponding abnormal cell. Healthy cells are not attacked. The cytotoxic T cells are conditioned to it.

The MHC class II protein complex also consists of two subunits, which consist of four domains in total. In contrast to the MHC class I protein complex, the subunits here are of the same size and anchored in the cell membrane. Similar to the MHC class I protein complex, a peptide is anchored in a cavity between the domains. This is a peptide from an extracellular protein. Like the T killer cells, the T helper cells are selected for endogenous proteins.

When peptides from foreign proteins are presented, the T helper cells come into action and ensure the formation of antibodies to bind the foreign proteins. While the immune response is cell-mediated in the MHC class I protein complex, it is a hormonally controlled process in the MHC class II protein complex.

Function & Tasks

The function of the major histocompatibility complexes is to recognize self and non-self proteins to ensure a targeted immune response. Everyone has their own specific proteins. The immune cells (T killer cells, T helper cells) are conditioned to these proteins. Defense reactions are carried out immediately against foreign proteins. This is necessary to protect the body from infection with bacteria , viruses or other pathogens. Through the presentation of the antigens on the cell membrane, the immune system develops a tolerance against the body’s own proteins.

Through a selection process, the immune cells learn to distinguish between diseased and healthy cells and between foreign and endogenous proteins. The presentation of the antigens serves this selection process. If the antigens deviate from the usual pattern, the affected cells or the foreign proteins are destroyed.

Via the MHC class I complex, the immune system is constantly on the lookout for degenerated proteins or viral infections. Altered and conspicuous cells are quickly eliminated. Via the MHC class II complex, the immune system reacts immediately with the formation of antibodies if an infection occurs or foreign protein penetrates the organism.


However, sometimes it happens that the immune system reacts against its own body. In this case, the tolerance of the immune cells to endogenous proteins is lost. The exact mechanism of this process is not yet fully understood.

The immune system usually attacks individual antigens. This leads to limited reactions against individual organs. In principle, however, the immune cells can attack any organ. Thus, the diseases of the rheumatic circle have an autoimmunological basis. Here the immune system attacks the connective tissue and the joints . There are permanent inflammatory reactions that can destroy the joint system. Some serious intestinal diseases such as ulcerative colitis are also autoimmune diseases . Another example of an autoimmune disease is what is known as Hashimoto’s thyroiditis .

In this disease, the immune system attacks the thyroid gland . First there is an overfunction and later an underfunction. Furthermore, allergies also represent a malfunction of the immune system. Here, the body reacts sensitively to normally harmless foreign proteins. As a rule, the immune system has learned to accept these proteins because they constantly act on the body. These include pollen, grass, animal hair or various dietary proteins. However, antibodies against these proteins are formed via the MHC class II complex. When confronted with the allergens, respiratory problems, skin rashes, headaches and a variety of other complaints often appear immediately.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.