MAJOR HISTOCOMPATIBILITY COMPLEX: CHARACTERISTICS, FUNCTIONS - BIOLOGY - 2025

The major histocompatibility complex or CMH (MHC, Major Histocompatibility Complex) is a term used to describe a complex genetic region and a set of protein products that participate in the regulation of immune responses in virtually all vertebrate animals.

Although it only represents a small portion of all its functions, the name "major histocompatibility complex" derives from the participation of these molecules in the acceptance or rejection of tissue grafts, a context in which they were studied for the first time almost 80 years ago. years.

Expression pattern of the major histocompatibility complex (Source: derivative work: Zionlion77 (talk) MHC_Class_1.svg: User atropos235 on en.wikipediaMHC_Class_2.svg: User atropos235 on en.wikipedia via Wikimedia Commons)

Currently it is already known that "naturally" speaking, the molecules encoded by this genetic region play an important role in the cellular immune response, specifically in that which has to do with T lymphocytes.

T lymphocytes belong to a line of blood cells and have their origin in the bone marrow, although they complete their maturation in an organ called the thymus, hence their name.

These cells participate in the activation of other similar cells, the B lymphocytes (antibody-producing cells), and are also directly involved in the elimination of cells infected with different pathogens.

The ability of T cells to recognize their action "targets" is given thanks to the participation of the proteins of the major histocompatibility complex, since it is these that "show" specific antigens that can be easily recognized by T cells, process that allows the development of its functions.

Characteristics: genes and proteins

The major histocompatibility complex (known in humans as the human leukocyte antigens or HLA) is a polymorphic gene complex that mainly encodes proteins that function as cellular receptors involved in the development of many of the immune system responses.

Although very few have to do with "histocompatibility" (the process by which they were named), there are more than 100 genes that belong to the major histocompatibility complex.

In humans, these are found on the short arm of chromosome 6 and are classified into three classes: class I, class II, and class III genes.

Class I genes

The class I genes of the major histocompatibility complex code for surface glycoproteins that are expressed in most nucleated cells in the human body. These proteins are involved in the presentation of cytotoxic T cell recognition antigens (foreign antigens).

It is important to remember that cytotoxic T lymphocytes play an important role in cellular immunity, specifically in what has to do with the elimination of cells that have been invaded by intracellular pathogens of parasitic, bacterial and viral origin.

Thus, the proteins encoded by MHC class I genes are directly involved in the body's defense against foreign intracellular agents.

MHC class I proteins bind to peptides derived from endogenous antigens (produced intracellularly by a pathogen) that have been processed in the cytosol and are subsequently degraded in the proteasome complex.

Antigen processing by class I major histocompatibility complex proteins (Source: MHC_Class_I_processing.svg: Scrayderivative work: Retama via Wikimedia Commons)

Once they are degraded, they are transported to the endoplasmic reticulum, which “packages” them and directs them towards the membrane in order to “load” or “bind” them to the MHC class I proteins, in order for the cell to be recognized by cytotoxic T lymphocytes.

In humans, all MHC genes are known as HLA genes (Human Leukocyte Antigens) and those of class I are: HLA-A, HLA-B, HLA-C, HLA-E, HLA-H, HLA- G and HLA-F.

The molecules encoded by these genes are somewhat different in terms of their amino acid sequence, however, their genes are expressed codominantly in all cells, that is, both the genes from the mother and those from the father are expressed at the same time. weather.

Class I and class II major histocompatibility complex proteins (Source: BQmUB2011048 via Wikimedia Commons)

Class II genes

The products encoded by these genes are specifically expressed in cells specialized in the "presentation" of antigens (antigen presenting cells or APCs), which can be macrophages, dendritic cells or B lymphocytes.

Antigens associated with the major histocompatibility complex proteins of class II are presented to helper T cells (helpers), in order to promote the activation of their immune functions.

Unlike class I proteins, these bind to peptides derived from exogenous antigens that are processed intracellularly; reason for which they are only expressed by cells capable of "eating" foreign or invading agents such as bacteria, for example.

Among the genes belonging to MHC class II in humans are HLA-DR, HLA-DP and HLA-DQ.

Class III genes

These genes code for proteins with immunological activity that are secreted, among which are some cytokines such as tumor necrosis factor (TNF), and some components of the complement system.

The region of the chromosome that codes for these genes lies between the coding loci of the class I and class II genes.

Allotypic polymorphism

All the molecules of the MHC complex present a high level of something that scientists have called “allotypic polymorphism” and that is related to the molecular variations of certain regions of the MHC proteins, which means that each person has an almost unique set of these molecules.

Features

The main function of the proteins encoded by the major histocompatibility complex has to do with the development of many of the adaptive immune responses of animals, responses that are usually triggered by the presence of pathogens or "foreign" conditions within the body..

These are proteins that are expressed on the plasma membrane (are surface receptors) of the nucleated cells of almost all vertebrate animals, with the exception of the enucleated (nucleusless) red blood cells of humans.

These receptors bind to peptides derived from endogenous or exogenous proteins and "present" them to be recognized by T cells or lymphocytes. Thus, the proteins of the MHC complex help the body to discriminate between what is its own and what is not., regulating the recognition of many infectious pathogens, for example.

Recognition of own and not own

The protein products of the MHC complex encoded by the class I and class II genes favor the process of distinguishing the self and the strange performed by T cells. This can easily be evidenced by the example of a patient receiving a transplant or a tissue graft.

How?

When an individual receives a foreign tissue, he receives with it cells that have class I or II molecules of the major histocompatibility complex that are not possessed by the rest of the individual's cells, so these are seen as foreign antigens and are "treated ”By the immune system as a foreign invasion.

References

1. Elhasid, R., & Etzioni, A. (1996). Major histocompatibility complex class II deficiency: a clinical review. Blood reviews, 10 (4), 242-248.
2. Kindt, TJ, Goldsby, RA, Osborne, BA, & Kuby, J. (2007). Kuby immunology. Macmillan.
3. Nagy, ZA (2013). A History of Modern Immunology: The Path Toward Understanding. Academic Press.
4. Pross, S. (2007). Major Histocompatibility Complex. Compr Pharmacol Ref, 1-7.
5. Thornhill, R., Gangestad, SW, Miller, R., Scheyd, G., McCollough, JK, & Franklin, M. (2003). Major histocompatibility complex genes, symmetry, and body scent attractiveness in men and women. Behavioral Ecology, 14 (5), 668-678.