Utilization of Antibody-Based Approaches for the Detection of SARS-CoV-2 and the Elucidation of Tyrosine Sulfation
Bibliographic record
Abstract
Adaptive immunity, characterized by diversity, specificity, and memory, exists in multicellular life forms. Alternative immune systems of different ancestral lineages, consequential of divergent and convergent evolution, are composed of distinct antigen recognition units but function with the same goal – to eliminate foreign invaders.Antigen-experienced B-lineage cells, memory B cells and plasma cells, are vital to long-lasting humoral immunity, and antibodies represent the major source of neutralizing agents against pathogens. The technological advancement of mankind has allowed the exploitation of antibodies as detection reagents in ex vivo systems for omics studies. Despite the centralism of antibody technology on mammalian, immunoglobulin-based antibodies, non-immunoglobulin alternatives such as the variable lymphocyte receptor B (VLRB) antibodies of jawless vertebrates have been employed in hopes of overcoming some of the structural and tolerogenic constraints faced by conventional antibodies. During the COVID-19 pandemic, we harnessed the VLRB antibody platform of the evolutionarily distant sea lamprey to develop diagnostic reagents for the novel causative coronavirus SARS-CoV-2. We isolated and characterzed VLRB B7, B33, and B39, which recognized the surface Spike (S)-protein of SARS-CoV-2, two of which exhibited neutralization potency. The adaptation of VLRB B39 tetramers formed the basis of a rapid, single-step SARS-CoV-2 detection assay. Previously, we utilized the VLRB antibody system to search for human memory B cell-specific biomarkers. Unexpectedly, we isolated the peculiar VLRB N8 that recognized human memory B cells and plasma cells in a manner correlating to HLA-I tyrosine sulfation. We then sought to determine the biological significance and to expand our understanding of tyrosine sulfation by examining the driving factors and lineage-specific profiles of tyrosine sulfation of membrane-bound proteins. Using a pan-sulfotyrosine antibody, we designed efficient, non-radioactive detection systems. We established lineage-specific expression patterns of cell-surface tyrosine sulfation among human immune cell populations. We then demonstrated the inducibility of cell-surface and HLA-I tyrosine sulfation under in vitro stimulatory conditions. We also identified a sulfotyrosine located on the HLA-I peptide-binding cleft and examined the biological relevance in terms of peptide binding, HLA-I expression, and HLA-I turnover. The results provided evidence for lineage-specific, activation-driven immune regulatory mechanisms for this understudied protein post-translational modification.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".