Measures of epitope binding degeneracy from T cell receptor repertoires
Bibliographic record
Abstract
Adaptive immunity is driven by specific binding of hyper-variable receptors to diverse molecular targets. The sequence diversity of receptors and targets are both individually known but, because multiple receptors can recognize the same target, a measure of the effective ‘functional’ diversity of the human immune system has remained elusive. Here, we show that sequence near-coincidences within T cell receptors that bind specific epitopes provide a new window into this problem, and allow the quantification of how binding probability co-varies with sequence. We find that near-coincidence statistics within epitope-specific repertoires imply a measure of binding degeneracy to amino acid changes in receptor sequence that is consistent across disparate experiments. Paired data on both chains of the heterodimeric receptor are particularly revealing since simultaneous near-coincidences are rare and we show how they can be exploited to estimate the number of epitope responses that created the memory compartment. In addition, we find that paired-chain coincidences are strongly suppressed across donors with different human leukocyte antigens, evidence for a central role of antigen-driven selection in making paired chain receptors public. These results demonstrate the power of coincidence analysis to reveal the sequence determinants of epitope binding in receptor repertoires.
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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 | 0.002 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".