HLA‐A*02:01 Presents Penicillin‐Modified Cysteinylated Peptides for T Cell Recognition
Bibliographic record
Abstract
BACKGROUND: A subset of patients experience immune-mediated hypersensitivity reactions towards β-lactam antibiotics, with drug-specific T cells implicated as one of the causative factors. The principal mechanism is thought to involve chemical haptenation of self-peptides, resulting in novel peptide drug-adducts that may trigger T cell recognition. Understanding the interactions between the β-lactam drug, the T cell receptor (TCR) and the peptide/human leukocyte antigen (pHLA) complex is critical to gain further mechanistic insights into these hypersensitivity reactions. This study aimed to 1) explore the array of haptenated ligands presented by HLA-A*02:01, 2) evaluate the repertoire of T cells involved in penicillin-induced reactions in a hypersensitive patient and 3) determine if a dominant penicillin-specific TCR clonotype recognises haptenated HLA peptides. METHOD: T cells expanded in the presence of BP, and the dominant TCR assayed for reactivity in a reporter cell line. RESULT: We report that BP modifies cysteine in preference to lysine residues within the HLA-A*02:01 immunopeptidome. This modification occurs via cysteine-drug conjugate formation, in conjunction with disulphide-mediated peptide modification, which has not previously been considered in the context of drug hypersensitivities. Furthermore, we demonstrate that a BP-specific TCR expanded from a patient reacts towards a reduction-sensitive epitope, consistent with a BP-cysteine adduct disulphide linked to a cysteine residue within the T cell epitope. CONCLUSION: Our study provides evidence that cysteine-penicillin adducts can be accommodated by HLA ligands with the potential to induce T cell-mediated allergic reactions.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".