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 B2 and B9 metabolites to MAIT cells. After the presentation of foreign antigen by MR1, MAIT cells secrete 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.
Molecular characteristics
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.
Development & presence in the body
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. Moreover, parenchymal and nonparenchymal liver cells are efficient antigen presenting cells for MAIT. 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 cell activation
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.