The human invariant chain p35 favors formation of nonameric complexes with MHC class II molecules (107.1)
Bibliographic record
Abstract
Abstract The invariant chain (Ii) associates with MHCII alpha beta (αβ) chains after biosynthesis. Although previous studies described (αβIi)3 nonameric complexes, a recent report suggested that Ii trimers could only bind a single MHCII heterodimer at once. (Roche et al, 1991, Koch et al, 2011) We have investigated this discrepancy in the context of two human Ii isoforms, p33 and p35. The latter includes an ER retention motif (RXR) that is masked by MHCII β cytoplasmic tail upon its association with Ii. Using transfected HEK293T cells and flow cytometry, we monitored ER egress of various combinations of MHCII and Ii variants. First, we showed that MHCII only masked Ii RXR motif if associated directly (in cis) to the p35 subunit. Second, our results indicated that while p33 homotrimers may exit the ER as pentamer with one MHCII, p35-p33 mixed-trimers require cis masking of every Ii RXR motif before egress, thereby favoring heptamers and nonamers formation. Indeed, sucrose gradient of cell extracts confirmed larger complexes with p35 compared to p33. Altogether, our data argue for a kinetic model in which p33 homotrimers are free to exit the ER at any time, independently of the number of associated MHCII. In contrast, ER retention of Ii trimer containing p35 allows for binding of multiple MHCII until every RXR motifs are inactivated.
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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) | 0.002 | 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".