Defining a novel domain of staphylococcal toxic shock syndrome toxin-1 critical for major histocompatibility complex class II binding, superantigenic activity, and lethality
Bibliographic record
Abstract
Staphylococcal toxic shock syndrome toxin-1 (TSST-1) is implicated in the pathogenesis of superantigen-mediated shock. We previously identified TSST-1 residues G31/S32 to be important for major histocompatibility complex (MHC) class II binding, as well as superantigenic and lethal activities. However, the site-directed TSST-1 mutant toxin, G31R, could still induce mitogenesis and low-level TNFalpha secretion, suggesting that additional MHC class II binding sites other than G31/S32 may exist. In the current study, a TSST-1-neutralizing monoclonal antibody, MAb5, was found to inhibit TSST-1 binding to human peripheral blood mononuclear cells, neutralize TSST-1-induced mitogenesis and cytokine secretion, and protect against TSST-1-induced lethality in vivo. Epitope mapping revealed that MAb5 bound to TSST-1 residues 51-56 (T(51-56); 51 YYSPAF 56 ). Peptide T(51-56) was synthesized and found to also inhibit TSST-1 binding to human monocytes as well as TSST-1-induced mitogenesis, cytokine secretion, and lethality in vivo. This T(51-56) epitope, located within the beta3/beta4 loop, and the previously identified G31/S32 epitope, within the beta1/beta2 loop of TSST-1, are separated within the primary sequence, but spatially juxtaposed to each other. Collectively, these findings suggest that a discontinuous epitope comprising of regions within both the beta1/beta2 and beta3/beta4 loops, are critical for MHC class II binding, and the consequent superantigenic and lethal activities of TSST-1.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 teacher head, 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".