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Record W3070953717 · doi:10.4049/jimmunol.2000249

A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02–Expressing Individuals

2020· article· en· W3070953717 on OpenAlexaff
Louise C. Rowntree, Thi H. O. Nguyen, Carine Farenc, Hanim Halim, Luca Hensen, Jamie Rossjohn, Tom Kotsimbos, Anthony W. Purcell, Katherine Kedzierska, Stéphanie Gras, Nicole A. Mifsud

Bibliographic record

VenueThe Journal of Immunology · 2020
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmune Cell Function and Interaction
Canadian institutionsInstitute of Infection and Immunity
FundersNational Health and Medical Research Council
KeywordsEpitopeImmunodominanceBiologyHuman leukocyte antigenT-cell receptorCD8T cellImmunologyVirologyAntigenImmune system

Abstract

fetched live from OpenAlex

Abstract EBV is one of the most common viruses found in humans and is prototypic of a persistent viral infection characterized by periods of latency. Across many HLA class I molecules, the latent-specific CD8+ T cell response is focused on epitopes derived from the EBNA-3 protein family. In the case of HLA-B*07:02 restriction, a highly frequent class I allele, the T cell response is dominated by an epitope spanning residues 379–387 of EBNA-3 (RPPIFIRRL [EBVRPP]). However, little is known about either the TCR repertoire specific for this epitope or the molecular basis for this observed immunodominance. The EBVRPP CD8+ T cell response was common among both EBV-seropositive HLA-B*07:02+ healthy and immunocompromised individuals. Similar TCRs were identified in EBVRPP–specific CD8+ T cell repertoires across multiple HLA-B7+ individuals, indicating a shared Ag-driven bias in TCR usage. In particular, TRBV4-1 and TRAV38 usage was observed in five out of six individuals studied. In this study, we report the crystal structure of a TRBV4-1+ TCR–HLA-B*07:02/EBVRPP complex, which provides a molecular basis for the observed TRBV4-1 bias. These findings enhance our understanding of the CD8+ T cell response toward a common EBV determinant in HLA-B*07:02+ individuals.

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: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0040.000

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 head0.044
GPT teacher head0.266
Teacher spread0.222 · 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

Citations14
Published2020
Admission routes1
Has abstractyes

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