CD4<sup>+</sup> T cell recognition of a highly conserved bacterial epitope of pneumolysin presented by a broadly expressed HLA allotype
Bibliographic record
Abstract
CD4 + T cell-mediated immunity against Streptococcus pneumoniae (pneumococcus) can protect against recurrent bacterial colonization and life-threatening invasive pneumococcal diseases (IPDs), including pneumonia, sepsis, and meningitis [1][2][3].With the emergence of new pneumococcal strains, there is an urgent need for vaccines that elicit broader population coverage against conserved pneumococcal antigens, irrespective of capsular serotype [2].Pneumolysin (Ply) is a key pneumococcal virulence factor belonging to a family of cholesterol-dependent cytolysins (CDCs) that disrupts host cell defence mechanisms and immune cell function.This cytotoxin is expressed by virtually all pneumococcal strains and pneumococcal carriage and infection induce natural immunity to Ply [3][4].Consequently, a detoxified form of this protein has been tested as a potential serotype-independent vaccine candidate to protect against IPD [5][6][7].In this study, we identified a highly immunogenic human CD4 + T cell epitope in Ply, presented by globally abundant HLA allotypes.We reveal that within the Ply epitope-specific T cell receptor (TCR) repertoire of healthy HLA-typed adults, there are a diverse array of public (shared between individuals) and private (individual-specific) TCRs.Moreover, the immunogenicity of the Ply epitope was underpinned by conserved residues in the core region of the peptide which enables cross-recognition of other bacterial pathogens expressing CDCs.Our structural data further showed that the HLA-Ply antigenic complex was engaged similarly by one representative public TCR and two distinct private TCRs.Taken together, these findings provide detailed molecular insights into CD4 + T cell-mediated recognition of a trans-species bacterial epitope, which may lead to the design of T cell-based interventions against infections involving S. pneumoniae as well as other CDC-producing bacterial pathogens.
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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) | 0.006 | 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".