A chimeric T cell receptor with superâsignaling properties
Why this work is in the frame
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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 TCRâαβ chains result in the activation of distinct signal transduction pathways by the CD3âγδϵ/ζ complex? To investigate which part of the TCRâβ chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCRâβ chain with the corresponding TCRâγ chain domains. We show here that hybridoma cells expressing a chimeric TCRâβ chain (βIII) containing intracellular and transmembrane TCRâγ amino acids, together with a wildâtype TCRâα (αwt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCRâαwt/βwt chains. This superâsignaling phenotype of the βIII chain was observed in two different TCRs. One specific for an alloantigen (IâAbm12) and one for an autoantigen (IâAb/MOG35-55). We found that this chimeric αwt/βIII TCR had normal association with CD3âγδϵ and ζ chains. To investigate the effect of the chimeric βIII chain in transgenic T cells, we made MOG35-55âspecific 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 superâsignaling 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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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 | 0.000 | 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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it