A biotin ligation assay reveals a complex proxiome for HLA-A2 and implicates MIA3 in cell surface expression of MHC class I molecules
Bibliographic record
Abstract
ABSTRACT Antigen presentation via MHC class I molecules (MHC-Is) is a turning point in the establishment of immune responses to endogenous threats, such as viruses. From their synthesis to their cell surface display, MHC-Is travel to many compartments, including the ER, Golgi, and endosomes. They come close to a plethora of molecules, some of which regulate directly or indirectly their folding and trafficking. While many of these proteins are well characterized, such as those found in the peptide loading complex, others remain to be discovered. The proxiome can be studied using proximity labeling assays, such as BioID, which relies on a biotin ligase fused to a bait of interest that biotinylates lysine residues on nearby proteins. These modified targets can then be purified and identified by mass spectrometry. By fusing BioID to the HLA-A2 cytoplasmic tail, we have applied this technique to the MHC-I antigen and identified 209 potential specific interactors in HEK293 cells, including PDZD8 (LYVAC) and MIA3 (Tango1). We knocked out MIA3 in HEK293 cells and measured an increase in the expression of MHC-I molecules, suggesting a role for this vesicle budding protein in the regulation of MHC-I trafficking. Notably, MHC-I crosslinking identified targets that connect reverse signalling to diverse metabolic processes. Altogether, our results underscore the promise of HLA-coupled biotin ligases as a powerful approach to dissect antigen presentation pathways.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 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".