ArticleThe Journal of experimental medicine2014
A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 197 papers.
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Who cites it
197 citing papers in PubMed, 300 citations in OpenAlex.
- Opsonization-Enhanced Antigen Presentation by MR1 Activates Rapid Polyfunctional MAIT Cell Responses Acting as an Effector Arm of Humoral Antibacterial Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2020Trial
- A common transcriptomic program acquired in the thymus defines tissue residency of MAIT and NKT subsets.The Journal of experimental medicine · 2019Trial
- Enumeration, functional responses and cytotoxic capacity of MAIT cells in newly diagnosed and relapsed multiple myeloma.Scientific reports · 2018Trial
- Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.Journal of immunology (Baltimore, Md. : 1950) · 2017Trial
- Abundant CD8British journal of cancer · 2026Article
- Review
- UcTCRp: a TCRβ-based framework for identifying and profiling MAIT- and iNKT-associated repertoire signals.Briefings in bioinformatics · 2026Article
- Article
- 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
- Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization.bioRxiv : the preprint server for biology · 2026Article
- Cytosolic delivery of bacterial metabolites by riboflavin transporters promotes MR1 antigen presentation and MAIT cell recognition.Immunology and cell biology · 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
- A miniaturized MR1 metabolite display system with native-like protein features.bioRxiv : the preprint server for biology · 2026Article
- Article
- Mutations outside the MR1 antigen binding groove differentially inhibit presentation of exogenous antigens.The Journal of biological chemistry · 2026Article
- The NF-κB transcription factor RelA directs mucosal-associated invariant T-cell development.Immunology and cell biology · 2026Article
- The antigen-presenting molecule MR1 binds host-generated riboflavin catabolites.The Journal of experimental medicine · 2026Article
- Mucosal-Associated Invariant T Cells in Rheumatic Diseases.Arthritis & rheumatology (Hoboken, N.J.) · 2026Review
137 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR β-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to structural alterations in MR1 that subsequently affected MAIT TCR recognition via conformational changes within the complementarity-determining region (CDR) 3β loop. Analysis of seven TRBV6-1(+) MAIT TCRs demonstrated how CDR3β hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and TRBV20(+) MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag-dependent manner, thereby modulating MAIT cell recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.