Molecular Basis of Ionic Suppression of ZAP-70 Dependent T Cell Receptor Activation
Bibliographic record
Abstract
Abstract Ionic imbalance in the tumor microenvironment alters the tumor-infiltrating T lymphocyte function. High extracellular K + suppresses T cell function by negatively regulating T cell receptor (TCR) signaling. In contrast, elevated extracellular Na + enhances T cell effector function by boosting the phosphorylation of TCR signaling modules. Here, we presented a mechanism explaining how the two monovalent cations differently regulate TCR function. At rest, high intracellular K + uncouples allosteric recruitment of ZAP-70, a key signaling module, to the TCR complex. The formation of antigen TCR complex induces K + efflux, causing spontaneous recruitment of ZAP-70 to the TCR. Increasing extracellular K + perturbs K + efflux and slows ZAP-70 recruitment to the TCR complex, even upon antigen binding. This leads to defects in T cell development and arthritis-like symptoms in juvenile mice. We conclude that K + dynamics is integral to T cell ligand discrimination and fundamental to turning off the signaling during T cell quiescence.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| 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; both teacher heads agree on what is shown here.
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".