Deimination exposes an immunodominant epitope of membrane‐associated myelin basic protein
Bibliographic record
Abstract
Multiple sclerosis (MS) is characterized by the active degradation of myelin in the central nervous system (CNS). The resultant lesions contain T cells, B cells, and macrophages that are reactive against myelin antigens. Myelin basic protein (MBP) is one of the candidate autoantigens. The primary role of MBP in the CNS is the maintenance of myelin compaction, serving as an adhesive molecule that brings together the apposing faces of the cytoplasmic leaflet of the myelin membrane. Deimination (conversion of arginine to citrulline) of MBP reduces the net positive charge of the protein and diminishes its interactions with the membrane. Moreover, the deiminated isoform is increased both in MS adult myelin and in developing normal myelin. We have studied the effect of deimination on the conformation and membrane‐association of the primary immunodominant epitope of murine MBP, V83‐T92, using site‐directed Cys‐substitution and spin labeling, EPR spectroscopy, and site‐specific proteolysis, of modified and unmodified membrane‐bound MBP variants. We show that arginine loss by quasi‐deimination (R→Q), at conserved deimination sites, causes the immunodominant epitope to form a more highly surface‐exposed and shorter amphipathic alpha‐helix. Moreover, cathepsin D digested the membrane‐associated modified MBP variant 3‐fold faster than the unmodified form that is predominant in healthy myelin. These results suggest a mechanism for myelin degradation and autoimmune pathogenesis in MS.
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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) | 0.001 | 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".