Bibliographic record
Abstract
HIV remains a global pandemic. No vaccine or cure exists. Most infected individuals progress to AIDS in the absence of antiretroviral therapy, but a rare group of elite controllers (<0.5% of the infected population) suppresses viremia to an undetectable level. HIV control is often associated with a robust host immune response, mediated by selected HLA alleles that elicit T cells against more conserved HIV peptide epitopes. T cell recognition of an infected cell is determined by its unique T cell receptor (TCR), which binds a virus-derived peptide presented on the cell surface by an HLA protein. An individual’s repertoire of TCR clones is large, but finite, and varies even among those who express the same HLA alleles. TCR sequence differences between controllers and non-controllers have been associated with variation in the antiviral activity of T cells, but few studies have explored this question comprehensively.\t My thesis project aims to identify TCR features that contribute to HIV control. To do this, I examined CD8+ T cell responses against the immunodominant HIV Gag TL9 (TPQDLNTML) epitope. TL9 is presented by HLA-B*42 and B*81, but only B*81 is associated with HIV control. I sequenced TCR from TL9-specific T cells, including dual-reactive cells associated with HIV control in B*42 individuals that recognized TL9 presented by both B*42 and B*81, and then conducted functional and structural assessments of selected TCR clones. TL9-specific TCR from B*81 individuals and dual-reactive TCR from B*42 individuals were highly enriched for TRBV12-3 gene usage. Furthermore, dual-reactive TCR from B*42 individuals were dominated by shared (or public) clones. Comprehensive functional analyses revealed that TCR from B*81 individuals and dual-reactive TCR from B*42 individuals displayed greater capacity to recognize TL9 variants, including common HIV escape mutations. Structural analyses of two dual-reactive TCR clones demonstrated an unusual peptide binding conformation driven by TRBV12-3 germline residues. My results demonstrate that clonal differences in the ability of TCR to recognize TL9 variants are associated with HIV control. Functional and structural data provide mechanistic insight into key features of more effective TL9-specific TCR. By highlighting the impact of TCR clonotype on HIV control, my results will inform development of new vaccine and therapeutic strategies.
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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 | 0.001 | 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 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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.
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".