High avidity and functionality of virus-specific CD8 T cells associated with protection during HCV reinfection (VIR2P.1168)
Bibliographic record
Abstract
Abstract The majority of acute hepatitis C virus (HCV) infection (75%) leads to chronicity and liver diseases. While 25% of infected individuals can naturally clear the infection, long-term protection is elusive and reinfection can occur. We have previously showed that protection from viral persistence upon HCV reinfection correlates with expansion of HCV specific T cells with increased breadth. Viral persistence was associated with limited expansion of virus specific T cells. CD8 T cell receptor (TCR) repertoire analysis showed that clonotypes associated with protection upon reinfection are recruited from the memory population, with focusing of the repertoire. We hypothesized that protective immune memory response is associated with selection of T cell clonotypes with the highest TCR avidity and a polyfunctional profile. We FACS sorted HCV-specific CD8 T cells to generate individual clones representative of clonotypes of high, medium or low frequency in the TCR repertoire. Tetramer titration assay showed that the TCR avidity correlated with the clonotype expansion in vivo upon reinfection. All clones showed a polyfunctional profile but the main function varied between clones. In conclusion, our results suggest that the main determinant for the expansion of memory HCV specific CD8+ T cells during HCV reinfection was the TCR avidity. The results of this study have implications for the development of vaccination regimens to boost generation and selection of such clonotypes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".