Stoichiometry and intracellular fate of TRIM-containing TCR complexes
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Bibliographic record
Abstract
BACKGROUND: Studying the stoichiometry and intracellular trafficking of the T cell antigen receptor (TCR) is pivotal in understanding its mechanisms of activation. The alphabetaTCR includes the antigen-binding TCRalphabeta heterodimer as well as the signal transducing CD3epsilongamma, CD3epsilondelta and zeta2 subunits. Although the TCR-interacting molecule (TRIM) is also part of the alphabetaTCR complex, it has not been included in most reports so far. RESULTS: We used the native antibody-based mobility shift (NAMOS) assay in a first dimension (1D) blue native (BN)-PAGE and a 2D BN-/BN-PAGE to demonstrate that the stoichiometry of the digitonin-solublized TRIM-containing alphabetaTCR is TCRalphabetaCD3epsilon2gammadeltazeta2TRIM2. Smaller alphabetaTCR complexes possess a TCRalphabeta CD3epsilon2gammadeltazeta2 stoichiometry. Complexes of these sizes were detected in T cell lines as well as in primary human and mouse T cells. Stimulating the alphabetaTCR with anti-CD3 antibodies, we demonstrate by confocal laser scanning microscopy that CD3epsilon colocalizes with zeta and both are degraded upon prolonged stimulation, possibly within the lysosomal compartment. In contrast, a substantial fraction of TRIM does not colocalize with zeta. Furthermore, TRIM neither moves to lysosomes nor is degraded. Immunoprecipitation studies and BN-PAGE indicate that TRIM also associates with the gammadeltaTCR. CONCLUSIONS: Small alphabetaTCR complexes have a TCRalphabeta CD3epsilon2gammadeltazeta2 stoichiometry; whereas those associated with one TRIM dimer are TCRalphabeta CD3epsilon2gammadeltazeta2TRIM2. TRIM is differentially processed compared to CD3 and zeta subunits after T cell activation and is not degraded. The gammadeltaTCR also associates with TRIM.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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