Differential antigenic requirements by diverse MR1-restricted T cells

R Seneviratna; SJ Redmond; HEG McWilliam; R Reantragoon; JA Villadangos; J McCluskey; DI Godfrey; NA Gherardin

Journal article

Differential antigenic requirements by diverse MR1-restricted T cells

R Seneviratna, SJ Redmond, HEG McWilliam, R Reantragoon, JA Villadangos, J McCluskey, DI Godfrey, NA Gherardin

Immunology and Cell Biology | WILEY | Published : 2022

DOI: 10.1111/imcb.12519

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Abstract

MHC-related protein 1 (MR1) presents microbial riboflavin metabolites to mucosal-associated invariant T (MAIT) cells for surveillance of microbial presence. MAIT cells express a semi-invariant T-cell receptor (TCR), which recognizes MR1–antigen complexes in a pattern-recognition-like manner. Recently, diverse populations of MR1-restricted T cells have been described that exhibit broad recognition of tumor cells and appear to recognize MR1 in association with tumor-derived self-antigens, though the identity of these antigens remains unclear. Here, we have used TCR gene transfer and engineered MR1-expressing antigen-presenting cells to probe the MR1 restriction and antigen reactivity of a rang..

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University of Melbourne Researchers

Samuel Redmond Author

Hamish McWilliam Author

Jose Villadangos Author

McCluskey James Author

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Grants

Awarded by University of Melbourne

Funding Acknowledgements

We thank staff from the flow cytometry facilities at the Department of Microbiology and Immunology at the Peter Doherty Institute. We thank Dr Lars Kjer-Nielsen for his role in the provision of C1R.MR1 mutants used in TCR ala-scan experiments, Associate Professor Andreas Behren (Olivia Newton-John Cancer Research Institute, Australia) for provision of human melanoma "LM-MEL" cell lines and Professor David Fairlie (University of Queensland, Australia) for the provision of 5-OP-RU and 5-amino-6-Dribitylaminouracil. This work was supported by the Australian Research Council (ARC; CE140100011 and DP170102471) and the National Health and Medical Research Council, Australia (NHMRC; 1113293, 1159932 and 2003192). NAG and HEGM were supported by ARC DECRA Fellowships (DE210100705 and DE170100575). DIG was supported by an NHMRC Senior Principal Research Fellowship (1117766). JAV was supported by an NHMRC Principal Research Fellowship (1154502).