MHC class II isotype-specific signaling complex on human B cells
Bibliographic record
Abstract
The highly polymorphic human major histocompatibility complex (HLA) class II molecules are acknowledged as signaling receptors although their coupling to signaling pathways is not yet fully elucidated. In this study, we investigated how HLA class II can be coupled to protein tyrosine kinase (PTK) signaling pathway in B cells and whether there might be differences depending on HLA class II isotype. Using the human B cell line Ramos, we demonstrate that CD19 and CD20 are two HLA class II-associated receptors that couple HLA class II to PTK signaling pathway where CD20 appears to be amajor component of HLA class II-mediated activation of Src kinases. Both HLA-DR and HLA-DP co-immunoprecipitate tyrosine-phosphorylated proteins (p-Tyr) whereas only activation through HLA-DR increases the tyrosine phosphorylation of these proteins. Indeed, in contrast to HLA-DR, cross-linking HLA-DP induces neither tyrosine phosphorylation nor homotypic adhesion, and induces ERK1/2 activation. Differential association of these isotypes with CD20 appears to be one of the mechanisms underlying their differential signaling. We provide an experimental evidence for a mechanism by which HLA class II molecules can be coupled to PTK signaling pathway and, underscores their isotypes differential signaling. Further investigation of these mechanisms is likely to provide new insights into how isotype specific MHC class II signaling can contribute to the regulation of the immune response.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.009 | 0.007 |
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; both teacher heads agree on what is shown here.
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".