A chimeric T cell receptor with superâsignaling properties
Bibliographic record
Abstract
A key question yet to be resolved concerns the structure and function relationship of the TCR complex. How does antigen recognition by the TCR‐αβ chains result in the activation of distinct signal transduction pathways by the CD3‐γδϵ/ζ complex? To investigate which part of the TCR‐β chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCR‐β chain with the corresponding TCR‐γ chain domains. We show here that hybridoma cells expressing a chimeric TCR‐β chain (βIII) containing intracellular and transmembrane TCR‐γ amino acids, together with a wild‐type TCR‐α (αwt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCR‐αwt/βwt chains. This super‐signaling phenotype of the βIII chain was observed in two different TCRs. One specific for an alloantigen (I‐Abm12) and one for an autoantigen (I‐Ab/MOG35-55). We found that this chimeric αwt/βIII TCR had normal association with CD3‐γδϵ and ζ chains. To investigate the effect of the chimeric βIII chain in transgenic T cells, we made MOG35-55‐specific TCR transgenic mice expressing either the αwt/βwt or chimeric αwt/βIII TCR. Similar to what was observed in hybridoma cells, transgenic αwt/βIII T cells showed a super‐signaling phenotype upon antigenic stimulation. Further studies may help us understand the effect of increased TCR signaling on autoimmunity and may lead to the identification of signaling molecules that can be targeted to stop the progression of autoimmune disorders such as multiple sclerosis
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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 | 0.001 | 0.001 |
| 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".