Abstract 1741 APOL7C control of protein antigen escape and cross-presentation in classical dendritic cells
Bibliographic record
Abstract
Cross-presentation is the essential process that links the detection of “danger” by dendritic cells to the generation of potent cytotoxic T cell responses against pathogens and cancer. Despite the obvious importance of cross-presentation, the molecular pathways driving cross-presentation remain unclear. It is believed that an essential step in cross-presentation is the transfer of phagocytosed protein antigens from within the phagosomes of dendritic cells to the cytosol. We have obtained exciting new evidence using bulk RNA sequencing and qPCR that upon exposure to “danger” signals, such as viral RNA, dendritic cells increase the expression of a poorly characterized pore-forming protein called apolipoprotein 7C (APOL7C). Utilizing live cell microscopy and immunofluorescence assays, we have found that APOL7C is recruited to phagosomal membranes and, strikingly, these phagosomes begin to show signs of breached membranes shortly after the arrival of APOL7C. APOL7C arrival on phagosomes and is accompanied by the arrival endolysosomal damage markers such as galectin 3 and correlates with the escape of luminal, membrane-impermeant fluorescent dyes and fluid-phase proteins to the cytosol. We have found that APOL7C-mediated phagosomal damage leads to protein antigen export from the phagosome to the cytosol where they can be processed for cross-presentation. This work will investigate the molecular mechanisms of APOL7C recruitment to phagosomes, elucidating pathways of protein antigen escape and processing for cross-presentation, and provide insight into new avenues of vaccine and cancer therapy development. Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Canadian Cancer Society, University of Calgary Veterinary Medicine.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.002 |
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".