Are our immunoglobulin V genes pre-adapted for recognizing pathogens: a 3-dimensional analysis (35.53)
Bibliographic record
Abstract
Abstract There is strong phylogenetic evidence that the immunoglobulin V genes that make a major contribution to the generation of diversity of our primary repertoire, are under selective pressure, perhaps by pathogens themselves. Here we report the X-ray crystallographic structural analysis and the consequent kinetic and thermodynamic characteristics of a representative of a subclass of human neutralizing antibodies that originate from a particular pair of Vh and Vk genes and that target a short linear epitope on a human pathogen, HCMV. By comparison of its characteristics with its putative germline ancestors, these studies demonstrate that conserved germline Vh and Vk genes encode key residues in CDR-1 and CDR-2 that are pre-adapted to provide the foundation for the generation of a high-affinity hypermutated antibody. They show that although somatic mutation results in improvements in complimentarity of the binding site, the antibody combining site of the neutralizing antibody does not conform to a lock and key model and retains considerable mobility that is stabilized by interaction with antigen. We speculate that this flexibility may enhance its effectiveness at neutralization of infectivity.
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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) | 0.002 | 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".