Molecular insights into MR1 ‐mediated T cell immunity: lessons learned and unanswered questions

Awad, Wael, Abdelaal, Mohamed R., Letoga, Victoria, McCluskey, James and Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 2025. Molecular insights into MR1 ‐mediated T cell immunity: lessons learned and unanswered questions. Immunological Reviews 331 (1) , e70033. 10.1111/imr.70033

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Abstract

The major histocompatibility complex class‐I related protein, MR1, is an evolutionarily conserved antigen presenting molecule that binds and displays organic metabolites to T cells, including mucosal associated invariant T (MAIT) cells and diverse MR1‐restricted T cells (MR1T). Structural studies have elucidated how MR1 can accommodate a range of chemical scaffolds that arise from foreign, synthetic, and self‐metabolites, although the full spectrum of metabolites that MR1 presents remains unclear. Presently, MAIT and MR1T cell recognition of MR1‐antigen complexes represents a new immune recognition paradigm and is emerging as a critical player in protective immunity, aberrant immunity, tumor immunity, and tissue repair. Moreover, the limited allelic variation of MR1 makes it an attractive therapeutic target. This review will address the unique features and capability of the MR1 molecule to display several classes of small molecules for T cell surveillance. We will also address the molecular basis underlying MAIT and MR1T TCR recognition of MR1‐binding ligands.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/
Publisher:	Wiley
ISSN:	0105-2896
Date of First Compliant Deposit:	14 May 2025
Date of Acceptance:	11 April 2025
Last Modified:	14 May 2025 09:30
URI:	https://orca.cardiff.ac.uk/id/eprint/178270

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