The unfolded protein response regulates MHC class I‐peptide presentation
Bibliographic record
Abstract
Cell stress elicits the unfolded protein response (UPR). UPR regulates the two processes that control MHC I‐peptide (MHC I‐p) presentation: protein translation and degradation. We therefore asked whether and how the UPR might modify MHC I‐p presentation. We evaluated the impact of the UPR on global MHC I expression and on presentation of the SIINFEKL peptide. EL4 cells stably transfected with bicistronic vectors coding HEL‐SIINFEKL protein variants were stressed with pharmacological agents or exposed to physiologically relevant stress, such as glucose deprivation, for various time durations. UPR intensity was monitored by western blot and/or qRT‐PCR analysis of BiP, XBP‐1 and phosphorylation of eIF2alpha. Expression of Kb and of Kb‐SIINFEKL was assessed by flow cytometry with or without prior acid peptide elution. UPR decreased surface expression of MHC, but did not affect its mRNA. Consequently, presentation of SIINFEKL by H2‐Kb molecules was decreased in chemically or physiologically stressed cells. During the UPR, cells preferentially presented MHC I‐p derived from the ER as opposed to the cytosol. Also, generation of de novo Kb‐SIINFEKL complexes was less affected for ER‐ vs. cytosol‐derived SIINFEKL. Our results show that the UPR affects MHC I‐p presentation and that it differentially regulates expression of ER‐ vs. cytosol‐derived peptides. Supported by the NCIC.
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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) | 0.003 | 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".