It is present on the surface of the cell. Major Histocompatibility Complex (MHC) is a group of genes that codes for proteins that help the immune system recognize foreign substances. MHC in different species is called out by different names.
In humans, the Major histocompatibility complex is called the Human Leukocyte Antigen ( HLA) system and the MHC in mice is the H-2 complex. Compatibility of donors for organ transplant and susceptibility to an autoimmune disease. It was discovered by Peter Gorer in 1930. MHC contains over 100 genetic complexes. It is MHC genes that determine the compatibility of donors and characteristics of immune response to give antigens. It also determines immune response such as overall immunological response. The main function of Mhc is to bring antigens to the cell surface to be recognized by T-cells. Majorly, Major Histocompatibility Complex is located on chromosome no 6 in humans and Chromosome 17 in mice.
Types of MHC:
- Type I MHC gene- It can be found on the surface of every cell.
- Type II gene- It is only limited to the cells of the immune system called macrophages and lymphocytes.
- Type III gene- This gene encodes different proteins, including immune function and it is also involved in inflammation.
There are two main categories of MHC molecules; type I and type II. These two types of MHC are membered bond glycoprotein, which is c
In humans, the location of the HLA complex is on the short arm of the chromosome. In quaternary structure Type I and type II molecules are very similar, but they differ in how these shapes are created via primary protein arrangements.
Structure and function of MHC:
MHC class I:
MHC class of the molecules, It is a single class 1 MHC molecule, consisting of 45 kilodaltons (kDa) which is associated with a single class I MHC molecule consisting of a 45-kilodalton (kDa) α chain associated noncovalently with a 12-kDa β2-microglobulin molecule. Unlike B-cells, T cells have a relationship with the Mhc molecule to receive antigen. There are three external domains in the α chain ( alpha 1, alpha 2 and alpha 3). Each is approximately 90 amino acids long. The alpha chain is further encoded by polymorphic genes, HLA-A, HLA-B and HLA-C.
- The basic unit of molecules of MHC are two polypeptide chains.
- It consists of one membrane-heavy chain which is also termed as spanning a chain, produced by MHC genes.
- The molecular weight of Heavy chains and light chains is 42 kDa and 12 kDa respectively.
- The alpha chain in the MHC molecule is a glycoside and is folded into three domains called alpha 1, alpha 2 and alpha 3 in which the alpha-3 domain associates non-covalently with beta2- microglobulin.
- In MHC class I, beta 2 microglobulin subunit is present which can only be recognised by CD8 co-receptors.
- To help the interaction of two alpha domains, there is growth between alpha 1 and alpha 2 regions.
- The groom’s floor plays an important role in presenting the antigen. The alpha-3 domain structurally resembles the constant domain of immunoglobulins.
- In MHC-1, bonded peptides have 8 to 10 chains of amino acids.
- It is present in every cell in the body, antigens that originate from cytoplasm contain self-proteins and foreign proteins which are produced within the cell. Production of protein can be monitored by killer T-cells.
- TCR also specifies in MHC, that if an antigen is brought apart from MHC then no recognition by TCR, such phenomena
- It is present in every cell, expressed in the lymphoid cell.
- For intracellular pathogens such as viruses and some bacteria, cellular immunity is mediated.
- In humans, the beta chain is non-polymorphic and in mice it is dimorphic.
- In MHC epitome is present which is recognized by antigen.
- Each MHC molecule has only one binding site but it can bind to different peptides to the same site but only at one time.
MHC- Class II:
In this class of MHC, molecules are composed of two polypeptide chains such as alpha and beta. The molecular weight of alpha-polypeptide is 34kDs. Here, alpha polypeptide folds into two domains, alpha 1 and alpha 2. B polypeptide also folds into two domains beta-1 and beta-2. Groves of alpha-1 and beta-1 domains are similar to MHC class I. Class II molecules have beta-1 and beta-2 subunits which are recognised by CD4 co-receptors. Like class I of MHC, MHC class II also gives rise to immunoglobulin-like regions. There are three pairs of Major Histocompatibility Complex class II alpha and beta chain genes, known as HLA-A, B, and C.
Glycoproteins of MHC class ii, are only present on specialised antigen-presenting immune cells. Proteins of MHC class II can be raised by professional antigen-presenting cells, dendritic cells and macrophages B cells. MHC class I and MHC class II have similar structures. They are encoded in the short arm of the human chromosome. MHC class- II genetic loci in humans( HLA) and In mice ( H-2). Immunoglobulin in MHC class II are alpha 2 and beta 2. In MHC class II alpha and beta chains are encoded. In MHC class I beta- microglobulin is not coded in MHC.
MHC- Class III :
molecules include several secreted proteins with immune functions such as Cytokines and heat shock proteins, but it doesn’t have any involved antigen presentation.
Certainly, some molecules of MHC are associated with an increased risk of autoimmune system and inflammatory systems. There is an indication of an association between MHC and autoimmunity, but its mechanism has not been fully understood yet. The main role of MHC is in antigen presentation, where the T-cell gets proper recognition.
Allorecognition is the ability of organisms to identify differences between the same species and another. Allorecognition is the cause of the rejection of transplanted tissue or organs. Immunosuppressants are drugs that reduce allorecognition. Understanding the target or function of MhC in all responses can be a future target for immunomodulation. The endogenous peptide is associated with the Major Histocompatibility Complex class I molecule which is recognized by Tc cells and the Exogenous peptide is associated with the Major Histocompatibility Complex class II molecule which is recognized by TH cells. The expression level of Major Histocompatibility Complex can be increased by cytokines (especially interferons)
