Cytotoxicity of human CD8+ T-cells and NK-cells is suppressed by an alternative NKG2D splice variant (90.19)
Bibliographic record
Abstract
Abstract NKG2D is an activating receptor crucial to diverse aspects of immune function. NKG2D-mediated cytotoxicity is utilized by human natural killer (NK) cells and CD8+ T-cells. Here, we functionally characterize an alternative splice variant of NKG2D in non-activated and activated human CD8+ T-cells, which is expressed as a membrane-anchored truncated protein that lacks the ligand-binding ectodomain. We found this truncated NKG2D (T/NKG2D) isoform to be unable to transmit an activating signal for cytolysis and its enforced expression to inhibit killing mediated by full-length NKG2D (F/NKG2D). Abundance of T/NKG2D transcripts is variable in non-activated and activated CD8+ T-cells, and inversely correlates with killing capacity. Co-immunoprecipitation showed that T/NKG2D pairs with DAP10 and heterodimerizes with F/NKG2D, suggesting that dominant negative regulation is due to formation of heterodimeric NKG2D receptor complexes incapable of binding to its ligands. Thus, competitive inhibition through the alternatively spliced NKG2D variant may constitute a novel mechanism that regulates NKG2D-mediated signaling and cytotoxicity in NK and CD8+ T-cells.
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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".