Human invariant chain Iip35 isoform expressed in Ii-deficient mice fully restores thymic selection (130.16)
Bibliographic record
Abstract
Abstract During biosynthesis, invariant chain (Ii) associates with MHC II molecules, prevents peptide binding in the endoplasmic reticulum (ER) and targets the complexes to the endocytic pathway. Iip35, a human-specific isoform, displays a cytoplasmic ER retention motif that is masked upon MHC II binding. Little is known on the role of this ER retention motif and we asked if Iip35 alone was capable of supporting the functions of Ii. We generated a Tg mouse expressing the human Iip35 isoform (Tgp35). Breeding with murine Ii deficient mice produced mice expressing only Iip35 (Tgp35/mIiKO). In these mice, Iip35 is highly expressed by about 30 % of B cells, 50% of splenic DC and 74% of IFNγ-induced macrophages. Interestingly, B cells expressing Iip35 were lost during the maturation process and not found in the T2 stage. We have demonstrated that Iip35 interacts with both murine Ii and MHC II. Also, we observed MHC II compacts forms typical of tight peptide binding. Iip35 partially rescued MHC II cell surface expression in mIiKO mice and was sufficient to fully restore thymic selection as judged by normal CD4+ T cell numbers in thymus and periphery. In contrast, as observed in mIiKO mice, no antigen-specific antibody production was observed in Tgp35/mIiKO following injection of Ova. Altogether, our results suggest that the Iip35 isoform is able to restore thymic selection but may not be sufficient to perform all Ii functions.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".