This document provides an overview of mucosal-associated invariant T cells (MAIT). It discusses that MAIT cells are a type of innate alpha beta T cell that express a semi-invariant T cell receptor and recognize bacterial vitamin B metabolites presented by MR1. The document outlines that MAIT cells make up a significant percentage of T cells in the human body, particularly in the mucosa and liver. Their functions include roles in early detection of bacterial infection through cytokine production and cytotoxic activity. The document also notes that MAIT cells have been found infiltrating various human tumor tissues.
2. Content
• Introduction
• MAIT cell
• History
• Percentage
• Function
• In health and disease
• MAIT and cancer
• References
3. Introduction
• Classically, T cells are subdivided into two major populations
based upon their TCR expression, namely alpha beta (αβ) T cells
and gamma delta (γδ) T cells.
• αβ T Cell divided into two types of cells Conventional αβ T cells
and αβ innate T cell
• Innate T cells act as a bridge between the innate and adaptive
immune systems.
4. Introduction …con
Conventional αβ T
cells
Innate αβ T cell
undergo T cell receptor (TCR) rearrangement and
thymic selection
Similarities
MHC I
MHC II
rapidly recognize foreign
pathogen signals .
- MR1, CD1d and CD1a
Differences
5. T cells upon their TCR
expression,
αβ T cell
Conventional
αβ T cells
Innate
αβ T cell
semi-
invariant
invariant
iNK T cell (MAIT)
γδ Tcell
6. MAIT cell..
• Mucosal-associated invariant T cells (MAIT).
• MAIT cells are either CD4–CD8– double negative (DN) .
• MAIT cells therefore have the capacity to act as innate effectors and as
enhancers of adaptive immunity.
• Mucosal-associated invariant T cells are represent the most abundant
innate T cells in humans. In adults, they display an effector phenotype,
whereas MAIT cells possess a naïve phenotype in cord blood.
• MAIT cells are more resistant to chemotherapy than other T-cell
populations.
• Mucosal-associated invariant T (MAIT) cells are very abundant in
humans and have antimicrobial specificity, but their functions remain
unclear.
7. History
• In 1993, Porcelli and colleagues performed the initial
identification of two subsets of unconventional T cells [1]. In
characterizing T cells lacking both the CD4 and CD8 co
receptors (double negative (DN) T cells) from human blood, two
populations were identified that appeared monoclonal in terms
of the expression of their T cell receptor (TCR).
• Each of these T cell subsets was found to express a singular
TCRa chain with limited sequence diversity specifically, One
subset (Va24) identified as invariant Natural Killer T cells
(iNKT) cells
• the second (Va7.2) would be named Mucosal associated invariant
T (MAIT) cells.
8. Percentage
• Human MAIT cells are remarkably abundant in blood,, gut and
liver, where they represent in blood up to 15% of DN T cells,
or 0.1–0.2% of all T cells.
• Other study showed that MAIT have a broad tissue distribution.
In human peripheral blood, Va7.2þ T cells are present at
frequencies ranging from <1% to about 10% of T cells.
• MAIT cells were found to be present at higher frequencies in
human liver tissue which represent up to 45% of the liver
lymphocytes
9. Function
The function of MAIT cells is unknown, but it is most certainly
closely related to their localization in the gut mucosa, which is
the largest tissue in contact with the outside environment.
1- MAIT cells could somehow be involved in the defense against
orally acquired pathogens.
2- MAIT cell function could involve interaction with DCs. MAIT
cells could perhaps influence the maturation state of DCs
.
10. Function…con
3- MAIT cells play role in early and rapid detection of bacterial
infection . They have antimicrobial function and help fight off
bacterial infection by responding to infected cells and producing
cytokines. The wide reactivity towards several microbial species,
including commensal organisms, implies a role for MAIT cells
in intestinal homeostasis.
4- Some studies suggest that MAIT cells have an immune function
in several immune disorders such as encephalitis , diabetes and
delayed type hypersensitivity.
11. In health and diseases
• In the absence of inflammation, MAIT cells participate in
the control of the commensal flora or food-borne antigens by
modulating APC function, or by regulating epithelial cell
homeostasis and secretion of antimicrobial molecules.
• In case of bacterial invasion, however, the provision of the
MR1-bound ligands to infected epithelial cells or APCs, in an
inflammatory context (production of IL-18, IL-12 or IL-23, for
which MAIT cells have receptors) induce production of IFN-g
by MAIT cells to prevent intracellular bacterial replication.
Under certain conditions, MAIT cells can also secrete granzymes
and other cytotoxic molecules to kill potential target cells, or IL-
17 to activate innate immune cells such as neutrophils.
12. MAIT and cancer
Study examined expression of the invariant TCRs of human
innate T cells in tumors such as malignant brain tumors and
kidney cancers.
• Va7.2-Ja33 of MAIT cells are examined in 19 kidney and brain
tumors.
Results showed that the invariant Va7.2-Ja33 TCR sequence in
biopsy samples of kidney cancer and brain tumors Va7.2- Ja33
were detected in 8 out of 11 kidney cancer and 6 out of 8 brain
tumors. The MAIT clonotype was more dominant than in the
peripheral blood (PB).
13. MAIT and cancer … con
• Tumor tissues obtained from 11 patients with clear cell kidney cancer
(left panel) and eight patients with brain tumor (right panel).
14. MAIT and cancer … con
Dissection :
• Invariant Va24-JaQ NKT and Va7.2-Ja33 MAIT cells could be
identified in tumor tissues. These data suggest that MAIT and
NKT cells are the major innate αβTCR lymphocyte subsets to
infiltrate human tumors and may indicate that presence of these
T cell subsets in tumors is not accidental but rather specific.
Indeed, the clonal dominance of MAIT and NKT was superior
to PB.
15. References
1. Treiner, E., Duban, L., Moura, I. C., Hansen, T., Gilfillan, S., & Lantz, O. (2005). Mucosal-
associated invariant T (MAIT) cells: an evolutionarily conserved T cell subset. Microbes and
infection, 7(3), 552-559.
2. Gold, M. C., & Lewinsohn, D. M. (2011). Mucosal associated invariant T cells and the immune
response to infection. Microbes and Infection, 13(8), 742-748.
3. Le Bourhis, L., Guerri, L., Dusseaux, M., Martin, E., Soudais, C., & Lantz, O. (2011). Mucosal-
associated invariant T cells: unconventional development and function. Trends in immunology, 32(5),
212-218.
4. Gao, Y., & Williams, A. P. (2015). Role of innate T Cells in anti-bacterial immunity. Frontiers in
immunology, 6.
5. Intestinal Immune System book by Soichiro Miura،Ryota Hokari
6. Peterfalvi, A., Gomori, E., Magyarlaki, T., Pal, J., Banati, M., Javorhazy, A., ... & Illes, Z. (2008).
Invariant Vα7. 2-Jα33 TCR is expressed in human kidney and brain tumors indicating infiltration
by mucosal-associated invariant T (MAIT) cells. International immunology, 20(12), 1517-1525.
7. Dusseaux, M., Martin, E., Serriari, N., Péguillet, I., Premel, V., Louis, D., ... & Lantz, O. (2011).
Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17–secreting T
cells. Blood, 117(4), 1250-1259.
