Team:Evry/Project/Mait

A new vaccinal vector targeting the MAIT Cells

Mucosal-associated invariant T (MAIT) cells were first described in 1999 and rapidly became a promisive way to carry out immunotherapy, in particular via recent findings revealing their unique anti-bacterial function. This cells represent the most abundant innate-like T-cell population within human beings, comprising up to ~5% of the total T-cell population. They are characterized by the expression of a semi-invariant TCR (Vα7.2-Jα33/12/20) that recognizes the MHC-like protein 1 (MR1), which presents a bacterial-derived ligand. Furthermore, MAIT cells have been associated with a number of disease settings, including bacterial infections, viral infections, and pro-inflammatory diseases such as multiple sclerosis and psoriasis. Thus, this large T lymphocyte population is likely to have an important role in human health.

General MAIT cells activation process

(1) Internalization of Salmonella by an antigen-presenting cell, either through infection or actively by phagocytosis. (2) Lysis of the bacteria, within endocytic compartments, releases 5-A-RU, which is converted to 5-OE-RU or 5-OP-RU and binds to and stabilizes MR1. (3) The stable MR1 translocates to the cell surface, where it is presented along with other co-stimulatory molecules, e.g., CD80 or CD86. (4) Bacterial components trigger pathogen recognition receptors (PRR), such as TLR8. (5) PRR triggering drives cytokine expression, such as IL-12, and the activation of the inflammosome, resulting in the release of active-IL-18. (6) MAIT cells are activated either by TCR recognition of MR1 in combination with co-stimulatory receptors, e.g., CD28, and/or by cytokines, e.g., IL-12 and IL18. (7) Activated MAIT cells express pro-inflammatory cytokines, e.g., IFNγ, TNFα, and IL-17. (8) These cytokines can directly act anti-bacterially, or recruit and stimulate other immune cells, e.g., neutrophils by IL-17. (9) Activation of MAIT cells upregulates perforin and granzyme B expression. (10) Theoretically, the degranulation of cytotoxic granules into infected cells (target cells), via recognition of MR1, could induce cell death and, thus, the potential clearance of infected cells.

RiboVax a new vaccinal vector to increase immunotherapy

MAIT cells

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