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Record W2505659580 · doi:10.1038/icb.2016.71

Maintenance of the EBV‐specific CD8<sup>+</sup> TCRαβ repertoire in immunosuppressed lung transplant recipients

2016· article· en· W2505659580 on OpenAlexaff
Thi H. O. Nguyen, Nicola L. Bird, Emma J. Grant, John J. Miles, Paul G. Thomas, Tom Kotsimbos, Nicole A. Mifsud, Katherine Kedzierska

Bibliographic record

VenueImmunology and Cell Biology · 2016
Typearticle
Languageen
FieldMedicine
TopicViral-associated cancers and disorders
Canadian institutionsInstitute of Infection and Immunity
FundersNational Institute of Allergy and Infectious DiseasesNational Health and Medical Research CouncilMedical Research Council
KeywordsT-cell receptorImmunologyBiologyCD8ImmunosuppressionT cellVirologyRepertoireAntigenImmune system

Abstract

fetched live from OpenAlex

Epstein‐Barr virus (EBV) is one of the most common viruses in humans, capable of causing life‐threatening infections and cancers in immunocompromised individuals. Although CD8+ T cells provide key protection against EBV, the persistence and dynamics of specific T‐cell receptor (TCR) clones during immunosuppression in transplant patients is largely unknown. For the first time, we used a novel single‐cell TCRαβ multiplex‐nested reverse transcriptase PCR to dissect TCRαβ clonal diversity within GLCTLVAML (GLC)‐specific CD8+ T cells in healthy individuals and immunocompromised lung transplant recipients. The GLC peptide presented by HLA‐A*02:01 is one of the most immunogenic T‐cell targets from the EBV proteome. We found that the GLC‐specific TCRαβ repertoire was heavily biased toward TRAV5 and encompassed five classes of public TCRαβs, suggesting that these clonotypes are preferentially utilized following infection. We identified that a common TRAV5 was diversely paired with different TRAJ and TRBV/TRBJ genes, in both immunocompetent and immunocompromised individuals, with an average of 12 different TCRαβ clonotypes/donor. Moreover, pre‐transplant GLC‐specific TCRαβ repertoires were relatively stable over 1 year post transplant under immunosuppression in the absence or presence of EBV reactivation. In addition, we provide the first evidence of early GLC‐specific CD8+ T cells at 87 days post transplant, which preceded clinical EBV detection at 242 days in an EBV‐seronegative patient receiving a lung allograft from an EBV‐seropositive donor. This was associated with a relatively stable TCRαβ repertoire after CD8+ T‐cell expansion. Our findings provide insights into the composition and temporal dynamics of the EBV‐specific TCRαβ repertoire in immunocompromised transplant patients and suggest that the early detection of EBV‐specific T cells might be a predictor of ensuing EBV blood viremia.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

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)0.0010.000

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 head0.006
GPT teacher head0.213
Teacher spread0.206 · 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 designObservational
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

Citations35
Published2016
Admission routes1
Has abstractyes

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