ArticleThe Journal of clinical investigation2025
MHC-related protein 1-restricted recognition of cancer via a semi-invariant TCR-α chain.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 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
- Allelic variation alters expression and antigen presentation of MR1 allomorphs.The Journal of biological chemistry · 2026Article
- Nonclassical MHC-I Molecules: Emerging Therapeutic Targets in Next-Generation Immunotherapy.MedComm · 2026Review
- Protocol for MR1-ligand cross-linking to discover metabolite antigens by proteomics.STAR protocols · 2026Article
- Optimized procurement of cancer-reactive T-cell receptors from clinical samples.Immunotherapy advances · 2026Article
- Unconventional guardians of the brain: MAIT cells as emerging players in glioblastoma immunity.Frontiers in immunology · 2026Review
- Systematic evaluation of MAIT and iNKT abundance as checkpoint blockade biomarkers.Frontiers in immunology · 2026Article
- MR1-ligand cross-linking identifies vitamin B6 metabolites as TCR-reactive antigens.Cell reports methods · 2025Article
- Antibacterial Activity of the p53 Tumor Suppressor Protein-How Strong Is the Evidence?International journal of molecular sciences · 2025Review
- Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions.Immunological reviews · 2025Review
- 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
Corrections and comments
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Authors and funding
24 authors.
Funding
Abstract
The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft. Here, we successfully cultured cancer-activated, MR1-restricted T cells from multiple donors and confirmed that they recognized a wide range of cancer types expressing the most common MR1*01 and/or MR1*02 allomorphs (over 95% of the population), while remaining inert to healthy cells including healthy B cells and monocytes. Curiously, in all but one donor these T cells were found to incorporate a conserved TCR-α chain motif, CAXYGGSQGNLIF (where X represents 3-5 amino acids), because of pairing between 10 different TRAV genes and the TRAJ42 gene segment. This semi-invariance in the TCR-α chain is reminiscent of MAIT cells and suggests recognition of a conserved antigen bound to K43.
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