Mucosal-associatedinvariant T cells (MAIT)

.Presented by:

Sumaiah Ali Alghamdi Submitted to:

Dr. Suliman Al Omar

Content • Introduction • MAIT cell• History • Percentage • Function• In health and disease • MAIT and cancer • References

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.

Introduction …con

Conventional αβ T cells

Innate αβ T cell

undergo T cell receptor (TCR) rearrangement and thymic selection

Similarities

MHC IMHC II

rapidly recognize foreign pathogen

signals .- MR1, CD1d and

CD1a

Differences

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

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.

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.

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

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

.

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.

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.

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).

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).

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.

References1. 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 Hokari6. 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.

Thanks