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bioRxiv · 10.1101/2025.03.20.644465

IL-21 selectively augments cytotoxic potential of antigen-activated MAIT cells

Wedlock, L. E.·Lamichhane, R.·Gilmer, S. C. L.·Vernall, A. J.·Ussher, J. E.
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Abstract

Mucosal-associated invariant T (MAIT) cells are unconventional cytotoxic T cells restricted by MHC class 1 related molecule, MR1. They are activated through their TCR by derivatives from microbial riboflavin synthesis or independently of TCR signalling via IL-12 and IL-18. Upon activation, MAIT cells upregulate cytotoxic molecules GrzB and perforin and lyse bacterially-infected cells. While cytokines act as co-stimulatory molecules that enhance MAIT cell activation, their specific role in regulating MAIT cell cytotoxicity remains unresolved. We show that the cytokine IL-21 enhances expression of GrzB and perforin on TCR or IL-12/IL-18-activated MAIT cells but has limited effect on MAIT cell cytokine production. Using a flow cytometry-based cytotoxic assay, we show priming MAIT cells with IL-21 enhances their ability to kill 5-OP-RU-treated B cell lines. We demonstrate a previously unexplored co-stimulatory role for IL-21 that selectively augments the cytotoxic potential of MAIT cells.

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Wedlock, L. E., Lamichhane, R., Gilmer, S. C. L., Vernall, A. J., Ussher, J. E.. 2025-03-25. IL-21 selectively augments cytotoxic potential of antigen-activated MAIT cells. https://doi.org/10.1101/2025.03.20.644465

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