The major histocompatibility complex is a collective term for a group of genes encoding the major histocompatibility antigens of animals. The human MHC is located on the short arm of human chromosome 6, and the mouse MHC is located on chromosome 17 of the mouse. The length of the MHC is approximately 4 x 10^6 bp. The human MHC is also called the HLA complex. The MHC of mice is called the H-2 gene. Due to the polygenic nature of MHC, it can be divided into MHC class I, MHC class II, and MHC class III genes, which encode MHC class I molecules, MHC class II molecules, and MHC III, depending on the structure, tissue distribution, and functional differences of the coding molecules. Class of molecules. The human MHC product is commonly referred to as HLA, the human leukocyte antigen.
MHC molecule
1. Types of MHC molecules
Different MHC-encoded products have different functions.
MHC class I (MHC I): Located on the surface of a general cell, it can provide some conditions in general cells. For example, if the cell is infected with a virus, the amino acid peptide of the outer membrane fragment of the virus is prompted to pass through the MHC to the outside of the cell. Can be identified by killer CD8+ T cells for culling.
MHC class II: only located on antigen-presenting cells (APC), such as macrophages. This kind of supply is external to the cell. If there is bacterial invasion in the tissue, the macrophage will be swallowed, and the bacterial fragments will be prompted by the MHC to help the T cells to initiate the immune response.
MHC class III: mainly encodes complement components, tumor necrosis factor, heat shock protein 70 and 21 hydroxylase genes.
2. Physiological significance of MHC molecules
MHC antigens were originally discovered as transplant antigens and are the major antigenic systems responsible for transplant rejection. This antigen is incompatible, which can cause the immune response of the receptor and reject the transplanted donor tissue. After the 1970s, MHC molecules also proved to have important immunophysiological functions.
MHC molecules are involved in antigen recognition during the immune response. In the 1970s, RM Zinkner Zeer and other mice found that killer T cells can kill the target cells infected with the same cells when killing the target cells infected with the virus, but have no killing effect on the infected target cells of different lines. The phenomenon is genetically restricted. It was subsequently confirmed that the killer T cells must be consistent with the MHC of the target cells to have a killing effect, so this phenomenon is also called MHC restriction.
This reveals the role of MHC in T cell recognition of heterologous antigens. Further studies have shown that T4 T cells are restricted by MHC class II molecules when recognizing heterologous antigens, while T8 T cells are restricted by MHC class I molecules when recognizing xenoantigens. This restrictive mechanism is that T cells, through their antigen recognition receptors, can simultaneously recognize new complex antigenic determinants formed by heterologous antigenic determinants and their own MHC molecules.
It has also been found that non-T cells such as peripheral blood B cells and monocytes can induce proliferative responses in certain autoreactive T cells in vitro, which is called self-mixed lymphocyte reaction (AMLR) and proves that this is a non- Caused by MHC class II antigens on T cells. Such autoreactive T cells may have an effect of enhancing or inhibiting immune function in vivo, thereby maintaining the immune stability of the body, and thus MHC molecules are also involved in immunomodulatory effects.
Studies have shown that MHC molecules also play an important role in the differentiation and maturation process of T cells in the thymus. In vitro studies have found that the removal of MHC class II antigen-positive stromal cells in the thymus inhibits the development of T4T cells, and the addition of monoclonal antibodies against MHC class II antigens in thymic culture cells can also prevent the development of T4 T cells. It is currently believed that MHC molecules play an important role in the formation of T cell self-tolerance and the production of T cell pools.
MHC gene
The understanding of the discovery, gene composition and function of MHC is based on mouse experiments. Therefore, it has been determined since the 1930s that the mouse MHC is located on chromosome 17, called the H2 complex. The H2 complex is composed of K region, I region, S region and D region, wherein the I region is further divided into two sub-regions, IA and IE, and the gene-encoded product is called the I region-associated antigen.
In 1958, Dausset et al found that there were different specific leukocyte antibodies in the serum of patients who received blood transfusions, multi-partum women and volunteers immunized with the same kind of leukocytes. These antibodies were used to identify many different specific white blood cell antigens. Human leukocyte antigen. Through genetic analysis of families and populations, it was found that human MHC is located on chromosome 6, called HLA complex.
All vertebrates have their own MHC. In addition to human HLA and mouse H2, the MHC of rhesus monkeys, chimpanzees, dogs, rabbits, guinea pigs, rats and chickens are called RhLA, ChLA, DLA, RLA, GpLA, AgBI (H-1I) and B.
In 1980, the Nobel Prize in Physiology or Medicine was awarded to Baruj Benacerraf, George D.Snell and Jean Dausset (three people). The study laid the foundation for the establishment of transplant immunology. Benaselav was an American medical scientist and immunologist who discovered immune response genes in MHC Tetramer when studying organ transplant rejection. Ir), pointing out that the immune phenomenon is controlled by this gene, and the immunology is pushed to the climax on the basis of genetics.
Snell is an American immunologist who proposed through tissue transplantation experiments in mice: The transplantability of tissues between different individuals is determined by specific antigens on the cell surface, ie histocompatibility antigen (also known as H antigen). , controlled by the H gene. This gene is present in a limited area of a chromosome called the major histocompatibility complex (MHC). Dosser, a French immunologist, discovered the human leukocyte antigen (HLA) and the HLA gene that determines these antigens, the H gene equivalent to mice; it also confirmed that humans and many other animals have MHC.
(1) Polygenicity: A gene complex consists of a plurality of closely adjacent gene loci whose encoded products have the same or similar functions.
For example: mouse H-2: chromosome 17: short arm of chromosome 6 (6P21.31), full length 3600-4000 kb, 224 gene loci (128 functional genes, 96 pseudogenes).
(2) Polymorphism: There are two or more alleles in the same HLA gene locus in the population.
The significance of MHC polymorphism:
1. Expanding the population's presentation of antigenic peptides is conducive to maintaining the survival and continuation of the population.
(The polymorphism of HLA products is mainly manifested in the difference in composition and sequence of amino acid residues in the antigen-binding groove)
2. It is not conducive to the choice of donors in organ transplantation.
It has been shown that MHC not only controls allograft rejection, but more importantly, it is closely related to the immune response, immune regulation and the production of certain pathological states. Thus, the complete concept of MHC refers to a group of closely linked genes that encode major histocompatibility antigens on a chromosome of a vertebrate, control mutual recognition between cells, and regulate immune responses.
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