Mucosal associated invariant T cell

Mucosal associated invariant T cells (MAIT cells) make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secretes pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease, although definitive evidence is yet to be published. Mucosal associated invariant T cells (MAIT cells) make up a subset of T cells in the immune system that display innate, effector-like qualities. In humans, MAIT cells are found in the blood, liver, lungs, and mucosa, defending against microbial activity and infection. The MHC class I-like protein, MR1, is responsible for presenting bacterially-produced vitamin B metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secretes pro-inflammatory cytokines and are capable of lysing bacterially-infected cells. MAIT cells can also be activated through MR1-independent signaling. In addition to possessing innate-like functions, this T cell subset supports the adaptive immune response and has a memory-like phenotype. Furthermore, MAIT cells are thought to play a role in autoimmune diseases, such as multiple sclerosis, arthritis and inflammatory bowel disease, although definitive evidence is yet to be published. MAIT cells constitute a subset of αβ T lymphocytes characterized by a semi-invariant T cell receptor alpha (TCRα) chain. The TCRα originates from the rearrangement of TCRα variable (V) and joining (J) gene segments TRAV1-2/TRAJ12/20/33 during VDJ recombination in the nucleus. However, TRAJ33 is expressed more often than TRAJ12 and TRAJ20. With little diversity in the TCRα chain, the TCR is more conserved in MAIT cells than in other T cell subsets. In addition, the TCRα chain can combine with a restricted number of possible TCRβ chains to form a functional MAIT cell TCR, further limiting TCR diversity. MAIT cells were initially specified as T cells that do not express the TCR co-receptors CD4 or CD8 on the cell surface. However, CD8+ MAIT cells have been recently observed. In humans, MAIT cells express high levels of CD161, interleukin-18 (IL-18) receptor, and chemokine receptors CCR5, CXCR6, and CCR6 on the cell surface. Additionally, as an indication of their memory-like phenotype in the periphery, mature MAIT cells express a CD44+, CD45RO+, CCR7−, CD62Llo phenotype. Like all T cell subsets, MAIT cells develop in the thymus. Here, T cells rearrange their TCRs and are subjected to TCR affinity tests as a part of positive selection and negative selection. However, rather than undergoing selection on MHC class I or II molecules, MAIT cells interact with the MHC class I-like molecule, MR1, on thymocytes. MR1 also serves as the antigen-presenting molecule outside of the thymus that binds to TCR and activates MAIT cells. MAIT cells display effector-like qualities before leaving the thymus, which is why they are often described as innate-like T cells in the peripheral tissue. This thymic development process is found in both mice and human MAIT cell populations. In healthy humans, MAIT cells are found in the lungs, liver, joints, blood, and mucosal tissues, such as the intestinal mucosa. In total, MAIT cells make up roughly 5% of the peripheral T cell population. MAIT cells are most common in the liver, where they usually comprise 20-40% of the T lymphocyte population. The total murine MAIT cell population is roughly ten times smaller than the human MAIT cell population. While MAIT cells display effector characteristics immediately out of the thymus, they may also undergo clonal expansion in the periphery and establish antigen memory. In this way, MAIT cells display both innate and adaptive characteristics. MAIT cells can be activated in ways that involve, and do not involve, MR1-mediated antigen presentation. However, MR1-independent and MR1-dependent activation elicit separate MAIT cell functions as part of an immune response. During MR1-independent activation against Mycobacteria, MAIT cells bind extracellular IL-12, which is often secreted by stressed macrophages. In response to IL-12, MAIT cells produce and secrete interferon-gamma (IFN-γ), a cytokine that activate macrophages, assists in the maturation of dendritic cells, and promotes the expression of MHC class II on antigen presenting cells. MAIT cells also secrete IL-17, an important pro-inflammatory cytokine, after binding IL-23. MAIT cells are also activated in a MR1-dependent manner, in which a MAIT cell's semi-invariant TCR binds to the MR1 protein presenting antigen. While most T cell subsets have TCRs that recognize peptide or lipid-based antigens in association with MHC or CD1, MAIT cells are unique in that they recognize small molecules created through the process of vitamin B2 (riboflavin) and B9 (folic acid) biosynthesis. The vitamin B2 related molecules that activate MAIT cells are chemically unstable, and undergo spontaneous degradation in water, although they have now been successfully chemically synthesised and isolated. Riboflavin and folic acid are both crucial components of the metabolic pathways in bacteria. When MR1 associates with these small molecules and becomes expressed on the surface of antigen-presenting cells, MAIT cell TCRs then bind to MR1, leading to MAIT cell activation, clonal expansion, memory, and an array of antimicrobial responses. While protective against some pathogens, MAIT cell activation can produce inflammatory cytokines that augment immunopathology and gastritis in chronic infection by Helicobacter pylori. MAIT cells are activated by compounds derived from bacterial vitamin B2 (riboflavin) biosynthesis. In 2014, the exact identity of the antigens were found to be the compounds 5-OP-RU (5-(2-oxopropylideneamino)-6-D-ribitylaminouracil) and 5-OE-RU (5-(2-oxoethylideneamino)-6-D-ribitylaminouracil). Both compounds are highly potent in activating MAIT cells, but are chemically unstable. Both have been chemically synthesised, stabilised and characterised in the solvent DMSO, allowing for the unstable compounds to be used as reagents for the study of MAIT cells.