PT  - JOURNAL ARTICLE
AU  - Phalora, Prabhjeet
AU  - Ussher, James
AU  - Hester, Svenja
AU  - Marchi, Emanuele
AU  - Mak, Jeffrey Y. W.
AU  - Fairlie, David P.
AU  - Klenerman, Paul
TI  - MR1 dependent MAIT cell activation is regulated by autophagy associated proteins
AID  - 10.1101/2022.09.20.508788
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.20.508788
4099  - http://biorxiv.org/content/early/2022/09/30/2022.09.20.508788.short
4100  - http://biorxiv.org/content/early/2022/09/30/2022.09.20.508788.full
AB  - 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 mediate MR1 antigen presentation have yet to be fully defined. We performed a mass spectrometry-based proteomics screen to identify MR1 interacting proteins and identified 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 trafficking pathway. This data implicates distinct roles for autophagy associated proteins in the regulation of MR1 activity and highlights the autophagy pathway as a key regulator of cellular antigen presentation.Competing Interest StatementThe authors have declared no competing interest.