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Record W4411583027 · doi:10.1016/j.jbc.2025.110416

A molecular basis underpinning TRBV28+ T-cell receptor recognition of MR1–antigen

2025· article· en· W4411583027 on OpenAlexaff
Wael Awad, Nicholas A. Gherardin, Lisa Ciacchi, Andrew N. Keller, Ligong Liu, David P. Fairlie, James McCluskey, Dale I. Godfrey, Jamie Rossjohn

Bibliographic record

VenueJournal of Biological Chemistry · 2025
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsInstitute of Infection and Immunity
FundersFaculty of Information Technology, Monash UniversityNational Institute of Allergy and Infectious DiseasesNational Health and Medical Research CouncilAustralian Research CouncilNational Institutes of HealthAustralian SynchrotronAustralian Nuclear Science and Technology OrganisationAustralian Cancer Research FoundationMedical Research Council
KeywordsUnderpinningT-cell receptorAntigenReceptorCell biologyChemistryMolecular recognitionComputational biologyBiologyBiochemistryImmunologyT cellImmune systemEngineering

Abstract

fetched live from OpenAlex

Mucosal-associated invariant T (MAIT) cells express a TRAV1-2 + T cell receptor (TCR) that recognises microbial vitamin B2-derivatives presented by the MHC class I-related molecule, MR1. Most MAIT TCRs incorporate a biased TCR-β repertoire, predominantly TRBV20-1 and TRBV6, but some utilise other TRBV genes, including TRBV28. A second conserved, albeit less frequent TRAV36 + TRBV28 + T cell population exhibits MAIT-like phenotypic features but use a markedly distinct mode of MR1-antigen-recognition compared to MAIT TCR-MR1 binding. Nevertheless, our understanding of how differing TCR gene usage results in altered MR1 binding modes remains incomplete. Here, binding studies demonstrated differential affinities and antigen-specificities between TRBV6 + and TRBV28 + MR1-restricted TCRs. Alanine-scanning mutagenesis on the TRAV36-TRBV28 TCR, revealed a strong dependence on germline-encoded residues within the highly selected CDR3α loop, similar to TRAV1-2- TRBV6 TCRs, and further alanine-scanning mutagenesis experiments demonstrate differential energetic footprints by these TCRs atop MR1. We determined the crystal structure of a MAIT TRAV1-2-TRBV28 + TCR-MR1-5-OP-RU ternary complex. This structure revealed a docking mode conserved amongst other TRAV1-2 + MAIT TCRs, with the TRBV28 -encoded TCR-β chain adopting highly distinct docking modes between the TRAV1-2 + and TRAV36 + TCRs. This indicates that the TCR-α chain dictates the positioning and role of the TCR-β chain. Taken together, these findings provide new molecular insights into MR1-Ag driven selection of paired TCR-α and TCR-β chains.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.241
Teacher spread0.223 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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