Display options
Cite
Seneviratna R, Redmond SJ, McWilliam HE, et al. Differential antigenic requirements by diverse MR1-restricted T cells. Immunol Cell Biol. 2021;doi: 10.1111/imcb.12519.
Seneviratna, R., Redmond, S. J., McWilliam, H. E., Reantragoon, R., Villadangos, J. A., McCluskey, J., Godfrey, D. I., & Gherardin, N. A. (2021). Differential antigenic requirements by diverse MR1-restricted T cells. Immunology and cell biology, . https://doi.org/10.1111/imcb.12519
Seneviratna, Rebecca, et al. "Differential antigenic requirements by diverse MR1-restricted T cells." Immunology and cell biology vol. (2021). doi: https://doi.org/10.1111/imcb.12519
Seneviratna R, Redmond SJ, McWilliam HE, Reantragoon R, Villadangos JA, McCluskey J, Godfrey DI, Gherardin NA. Differential antigenic requirements by diverse MR1-restricted T cells. Immunol Cell Biol. 2021 Dec 23; doi: 10.1111/imcb.12519. Epub 2021 Dec 23. PMID: 34940995.
Copy Download .nbib Format: NLM
Share it on

Immunol Cell Biol. 2021 Dec 23; doi: 10.1111/imcb.12519. Epub 2021 Dec 23.

Differential antigenic requirements by diverse MR1-restricted T cells.

Immunology and cell biology

Rebecca Seneviratna, Samuel J Redmond, Hamish E McWilliam, Rangsima Reantragoon, Jose A Villadangos, James McCluskey, Dale I Godfrey, Nicholas A Gherardin

Affiliations

  1. Department of Microbiology & Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, VIC 3000, Australia.
  2. Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, 3010, Australia.
  3. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
  4. Present address: Immunology Division, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  5. Centre of Excellence in Immunology and Immune-mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

PMID: 34940995 DOI: 10.1111/imcb.12519

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 recognises 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 tumour cells and appear to recognise MR1 in association with tumour-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 (APCs) to probe the MR1-restriction and antigen reactivity of a range of MR1-restricted TCRs, including model tumour-reactive TCRs. We confirm MR1 reactivity by these TCRs, show differential dependence on lysine at position 43 of MR1 (K43), and demonstrate competitive inhibition by MR1 ligand 6-formylpterin (6-FP). TCR-expressing reporter lines, however, failed to recapitulate the robust tumour specificity previously reported, suggesting an importance of accessory molecules for MR1-dependent tumour-reactivity. Finally, MR1-mutant cell lines showed that distinct residues on the α1/α2 helices were required for TCR-binding by different MR1-restricted T cells and suggested central but distinct docking modes by the broad family of MR1-restrictd αβ TCRs. Collectively, these data are consistent with recognition of distinct antigens by diverse MR1-restricted T cells.

This article is protected by copyright. All rights reserved.

Keywords: MAIT; MR1; T cell receptor; antigen processing and presentation

Publication Types