Targeting the TIGIT/CD226/CD96 Signaling Axis using the IgV Domain of PVR
Bibliographic record
Abstract
PVR (poliovirus receptor) functions as a ligand that signals through TIGIT and CD96 to induce suppression of T-cell and NK-cell responses and binds to CD226, resulting in a co-stimulatory signal. PVR and its immune-cell receptors have been implicated in several diseases including cancer and autoimmune disorders. Therefore, my thesis focused on engineering a soluble version of the PVR extracellular domain that could serve to modulate immune responses responsible for such diseases. We developed vdPVR-Fc by fusing the murine IgV binding region of PVR to the Fc-domain of human IgG1. vdPVR-Fc bound to recombinant forms of its receptors TIGIT, CD96 and CD226 with similar low nanomolar affinities. Additionally, vdPVR-Fc could suppress murine T-cell activity ex-vivo. Importantly, vdPVR-Fc suppressed inflammatory responses in-vivo by reducing disease severity in murine models of psoriasis and colitis. Collectively, these results demonstrate that the minimal IgV domain of PVR is sufficient to dampen T-cell mediated immune responses.
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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".