The pathogenicity of self-antigen decreases at high levels of autoantigenicity: a computational approach
Bibliographic record
Abstract
Recent experimental evidence suggests that antigenic stability facilitates antigen shuttling from target tissue to dendritic cells (DCs), enabling cross-priming of naive T cells. On the other hand, antigenic stability affects the efficiency of peptide-MHC (p-MHC) complex formation, altering a target cell's susceptibility to killing by the resulting CTLs. Using a mathematical model, we show how antigenic stability and p-MHC production efficiency interplay in autoantigenicity and pathogenic potential of target cell proteins in autoimmune disease. We consider protein allocated to both rapidly degraded versus stable functional pools [fractions f, 1 - f], contributing, with relative efficiency eta, to p-MHC presentation on a target cell, as well as to cross-presentation on a DC; we analyze the combined effect of these parameters. Our results suggest that autoantigenicity and pathogenicity (ability to elicit T cell activation versus target cell lysis) are not equivalent and that pathogenicity peaks at low to moderate levels of autoantigenicity.
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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 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".