ArticleProceedings of the National Academy of Sciences of the United States of America2024
MR1 presents vitamin B6-related compounds for recognition by MR1-reactive T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Select intratumoral riboflavin-auxotrophicProceedings of the National Academy of Sciences of the United States of America · 2026Article
- The MHC-I related protein 1 MR1 can bind host purine catabolites.The Journal of biological chemistry · 2026Article
- Antigenic stimulation in conjunction with cytokine is required for mediating IL-17A production in human MAIT cells.Scientific reports · 2026Article
- Human neonatal MR1T cells have more diverse TCR repertoires but reduced bacterial recognition than adult MR1T cells.Nature communications · 2026Article
- Allelic variation alters expression and antigen presentation of MR1 allomorphs.The Journal of biological chemistry · 2026Article
- Role of Donor Unrestricted T Cells (DURTs) in TB Host Defense: Implications for Novel TB Vaccine Development.Vaccines · 2026Review
- Article
- From Fly to Human: Translational Relevance ofInternational journal of molecular sciences · 2026Review
- The antigen-presenting molecule MR1 binds host-generated riboflavin catabolites.The Journal of experimental medicine · 2026Article
- Antigenic stimulation in conjunction with cytokine is required for mediating IL-17A production in human MAIT cells.bioRxiv : the preprint server for biology · 2026Article
- Integration of Multi-Omics Data Identifies the Role of the Selenium-Related Gene PNPO and Pre-exhausted CD127Cancer informatics · 2026Article
- Unconventional guardians of the brain: MAIT cells as emerging players in glioblastoma immunity.Frontiers in immunology · 2026Review
- Single-cell transcriptomic insights into the immune heterogeneity of immune checkpoint inhibitors related organ toxicities.Frontiers in immunology · 2026Review
- Multifaceted role of the vitamin B6 pathway in cancer: metabolism, immune interaction, and temporal and spatial regulation.Genes & development · 2025Review
- MR1-ligand cross-linking identifies vitamin B6 metabolites as TCR-reactive antigens.Cell reports methods · 2025Article
- Mucosal-associated invariant T-cells in pulmonary pathophysiology.Current opinion in pulmonary medicine · 2025Review
- Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions.Immunological reviews · 2025Review
- Human Neonatal MR1T Cells Have Diverse TCR Usage, are Less Cytotoxic and are Unable to Respond to Many Common Childhood Pathogens.bioRxiv : the preprint server for biology · 2025Article
- Unconventional T cells in anti-cancer immunity.Frontiers in immunology · 2025Review
- Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor.Frontiers in immunology · 2025Article
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22 authors.
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Abstract
The major histocompatibility complex class I related protein (MR1) presents microbially derived vitamin B2 precursors to mucosal-associated invariant T (MAIT) cells. MR1 can also present other metabolites to activate MR1-restricted T cells expressing more diverse T cell receptors (TCRs), some with anti-tumor reactivity. However, knowledge of the range of the antigen(s) that can activate diverse MR1-reactive T cells remains incomplete. Here, we identify pyridoxal (vitamin B6) as a naturally presented MR1 ligand using unbiased mass spectrometry analyses of MR1-bound metabolites. Pyridoxal, and the related compound, pyridoxal 5-phosphate bound to MR1 and enabled cell surface upregulation of wild type MR1*01 and MR1 expressing the Arg9His polymorphism associated with the MR1*04 allotype in a manner dependent on Lys43-mediated Schiff-base formation. Crystal structures of MR1*01 in complex with pyridoxal and pyridoxal 5-phosphate showed how these ligands were accommodated within the A-pocket of MR1. T cell lines transduced with the 7.G5 TCR, which has reported "pan-cancer" specificity, were specifically activated by pyridoxal presented by antigen-presenting cells expressing MR1*01 and MR1 allotypes bearing the less common Arg9His polymorphism. 7.G5 T cells also recognized, to a lesser extent, pyridoxal 5-phosphate and, importantly, recognition of both vitamers was blocked by an anti-MR1 antibody. 7.G5 TCR reactivity toward pyridoxal was enhanced when presented by the Arg9His polymorphism-bearing MR1 allotypes. Vitamin B6, and vitamers thereof, have been associated with various cancers, and here we describe a link between this ligand, MR1, and its allomorphs, and the pan-cancer 7.G5 TCR. This work identifies an MR1 ligand that can activate a diverse MR1-restricted TCR.
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