An immunodominant epitope of myelin basic protein is an amphipathic α-helix
Bibliographic record
Abstract
Myelin basic protein (MBP) is a candidate autoantigen in multiple sclerosis (MS). Its dominant antigenic epitope for both B cells and T cells is residues 85–96 (human sequence). Contradictory predictions of secondary structure in this region have been made. We used molecular dynamics and site-directed cysteine-specific spin labeling to show that this segment forms a transient amphipathic a-helix, which is stabilized in 30% trifluoroethanol and on binding to a myelin-like lipid surface. When bound to the membrane, the a- helix is partially embedded in the lipid bilayer and tilted at an angle of 9°. Key contact points for antibody recognition, the two phenylalanines at positions 89–90 and lysine 91, are embedded in the bilayer and thus would be sequestered from antibody. The central lysine 91 is positioned so that its positively charged side chain protrudes out of the bilayer into the polar head group region to interact with the polar lipid head groups. Antibody binding to this epitope of membrane-bound MBP would occur only if this region transiently dissociates from the membrane. This is more likely to occur for the deiminated charge isomer of MBP (C8), which is increased in MS myelin, than for the most positively charged form (C1), since deimination of six arginines of MBP caused dissociation of the C-terminal end of MBP from the bilayer. Acknowledgment: This work was supported by grants from CIHR, NSERC, the MS Society of Canada, and the US Public Health Service.
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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 | 0.001 |
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".