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bioRxiv · 10.1101/2022.09.20.508788

MR1 dependent MAIT cell activation is regulated by autophagy associated proteins

Phalora, P.·Ussher, J. E.·Hester, S.·Marchi, E.·Mak, J. Y. W.·Fairlie, D. P.·Klenerman, P.
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Abstract

The antigen presenting molecule, MR1, presents microbial metabolites to MAIT cells, a population of innate-like, anti-microbial T cells. It also presents an unidentified ligand to MR-1 restricted T cells in the setting of cancer. The cellular co-factors that regulate MR1 antigen presentation have yet to be fully defined. We performed a mass spectrometry-based proteomics screen to identify MR1 interacting proteins and discovered the selective autophagy receptor SQSTM1/p62. CRISPR-Cas9-mediated knock out of SQSTM1/p62 increased MAIT cell activation in the presence of E.coli but not the synthetic ligand 5-OP-RU whereas depletion of Atg5 and Atg7, key autophagy proteins, increased MAIT activation irrespective of the ligand used. This regulation appears to occur at an early step in the MR1 trafficking pathway. This data implicates distinct roles for autophagy associated proteins in the regulation of MR1 activity and highlights the contribution of the autophagy pathway to regulation of cellular antigen presentation.

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Phalora, P., Ussher, J. E., Hester, S., Marchi, E., Mak, J. Y. W., Fairlie, D. P., Klenerman, P.. 2022-09-21. MR1 dependent MAIT cell activation is regulated by autophagy associated proteins. https://doi.org/10.1101/2022.09.20.508788

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