TCR subunit specificity of CTLA-4-mediated signaling
Bibliographic record
Abstract
Cytotoxic T-lymphocyte-associated antigen (CTLA)-4 is an activation-induced receptor that down-regulates T cell responses by antagonizing B7-dependent costimulation and/or by transducing a negative signal. The mechanism of CTLA-4-mediated negative signaling is unknown. Recently, it has been postulated that CTLA-4 inhibits T cell activation by causing specific dephosphorylation of the T cell receptor (TCR)-zeta chain of the antigen-receptor complex through an lck-dependent recruitment of the Src homology-2-containing tyrosine phosphatase-2. To test this hypothesis, we generated stably transfected T cell clones expressing doxycycline-inducible CTLA-4 with CD25:TCR-zeta (CD25-zeta) or CD25:CD3-epsilon (CD25-epsilon) fusion proteins. In these clones, ligation of CD25-zeta or of CD25-epsilon with antibodies against CD25 induced full T cell activation, as illustrated by extracellular signal-regulated kinase (ERK) activation and interleukin (IL)-2 production. More importantly, coligation of CTLA-4 with CD25-zeta or of CTLA-4 with CD25-epsilon in the respectively transfected clones inhibited ERK activation and IL-2 production, demonstrating that CTLA-4 does not specifically inhibit signals from TCR-zeta but can also inhibit signals from CD3-epsilon. Our results suggest that the target specificity of CTLA-4 is determined by its coligation with any given transmembrane receptor rather than by its intracellular mediators.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".