MHC class III is a group of proteins belonging the class of

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

(MHC). Unlike other MHC types such as

MHC class I MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules (the other being MHC class II) and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on plat ...

and

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells, ...

, of which their structure and functions in

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

are well defined, MHC class III are poorly defined structurally and functionally. They are not involved in

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

binding (the process called

antigen presentation Antigen presentation is a vital immune process that is essential for T cell immune response triggering. Because T cells recognize only fragmented antigens displayed on cell surfaces, antigen processing must occur before the antigen fragment, now ...

, a classic function of MHC proteins). Only few of them are actually involved in immunity while many are signalling molecules in other cell communications. They are mainly known from their genes because their gene cluster is present between those of class I and class II. The gene cluster was discovered when genes (specifically those of complement components C2, C4, and

factor B Complement factor B is a protein that in humans is encoded by the ''CFB'' gene. Function This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single cha ...

) were found in between class I and class II genes on the short (p) arm of human chromosome 6. It was later found that it contains many genes for different signalling molecules such as tumour necrosis factors (TNFs) and

heat shock proteins Heat shock proteins (HSP) are a family of proteins produced by cells in response to exposure to stressful conditions. They were first described in relation to heat shock, but are now known to also be expressed during other stresses including expo ...

. More than 60 MHC class III genes are described, which is about 28% of the total MHC genes (224). The region within MHC class III gene cluster that contains genes for TNFs is also known as MHC class IV or inflammatory region. In contrast to other MHC proteins, MHC class III proteins are produced by liver cells (

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s) and special white blood cells (

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

s), among others.

Gene structure

MHC class III genes are located on chromosome 6 (6p21.3) in humans. It covers 700 kb and contains 61 genes. The gene cluster is the most gene-dense region of the human genome. They are basically similar with those of other animals. The functions of many genes are yet unknown. Many

retroelement Retrotransposons (also called Class I transposable elements or transposons via RNA intermediates) are a type of genetic component that copy and paste themselves into different genomic locations (transposon) by converting RNA back into DNA through ...

s such as

human endogenous retrovirus Endogenous retroviruses (ERVs) are endogenous viral elements in the genome that closely resemble and can be derived from retroviruses. They are abundant in the genomes of jawed vertebrates, and they comprise up to 5–8% of the human genome ( ...

(HERV) and

Alu element An Alu element is a short stretch of DNA originally characterized by the action of the ''Arthrobacter luteus (Alu)'' restriction endonuclease. ''Alu'' elements are the most abundant transposable elements, containing over one million copies disp ...

s are located in the cluster. The region containing genes '' STK19(G11)/C4/Z/ CYP21/X/Y'', varying in size from 142 to 214 kb, is known as the most complex gene cluster in the human genome.

Diversity

MHC class III genes are similar in humans, mouse, frog (''

Xenopus tropicalis The western clawed frog (''Xenopus tropicalis'') is a species of frog in the family Pipidae, also known as tropical clawed frog. It is the only species in the genus ''Xenopus'' to have a diploid genome. Its genome has been sequenced, making it a ...

''), and

gray short-tailed opossum The gray short-tailed opossum (''Monodelphis domestica'') is a small South American member of the family Didelphidae. Unlike most other marsupials, the gray short-tailed opossum does not have a true pouch. The scientific name ''Monodelphis'' is ...

, but not all genes are common. For example, human ''

NCR3 Natural cytotoxicity triggering receptor 3 is a protein that in humans is encoded by the ''NCR3'' gene. NCR3 has also been designated as CD337 (cluster of differentiation 337) and as NKp30. NCR3 belongs to the family of NCR membrane receptors toget ...

'', ''MIC'' and ''MCCD1'' are absent in mouse. Human ''NCR3'' and ''

LST1 Leukocyte-specific transcript 1 protein is a protein that in humans is encoded by the ''LST1'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''g ...

'' are absent in opossum. However, birds (chicken and quail) have only a single gene, which codes for a complement component gene (C4). In fishes, the genes are distributed in different chromosomes.

References

{{Reflist Immune system Cell signaling Genes on human chromosome 6 Cytokines Heat shock proteins