β2-Glycoprotein I-specific T Cells Are Associated with Epitope Spread to Lupus-related Autoantibodies
Bibliographic record
Abstract
Systemic lupus erythematosus (SLE) is a prototypic model for B cell epitope spread in autoimmunity. Autoantibodies to numerous and molecularly distinct self-antigens emerge in a sequential manner over several years, leading to disease manifestations. Among the earliest autoantibodies to appear are those targeting the apoptotic cell-binding protein β 2 -glycoprotein I (β 2 GPI). Notably, mice immunized with β 2 GPI and LPS display a remarkably similar pattern of autoantibody emergence to that seen in human SLE. Here, we used this model to investigate whether epitope spread to SLE-related autoantibodies is associated with a unique or limited β 2 GPI-specific T cell response. We ask whether MHC class II haplotype and its associated T cell epitope restriction impact epitope spread to SLE-related autoantibodies. We found that β 2 GPI/LPS-immunized mice produced similar SLE-related autoantibody profiles regardless of their β 2 GPI T cell epitope specificity or MHC class II haplotype. Although β 2 GPI T cell epitope specificity was clearly determined by MHC class II haplotype, a number of different β 2 GPI T cell epitopes were associated with epitope spread to SLE-related autoantibodies. Notably, one β 2 GPI T cell epitope (peptide 23, NTGFYLNGADSAKCT) was also recognized by T cells from an HLA-DRB1*0403 + autoimmune patient. These data suggest that the generation of a β 2 GPI-reactive T cell response is associated with epitope spread to SLE-related autoantibodies, independent of epitope specificity or MHC class II restriction. On the basis of these findings, we propose that factors enabling a β 2 GPI-reactive T cell response may predispose individuals to the development of SLE-related autoantibodies independent of their MHC class II haplotype. Background Systemic lupus erythematosus (SLE)-related autoantibodies are of unknown origin but target multiple apoptotic cell-derived antigens. Results T cell responses to multiple epitopes on β 2 -glycoprotein I (β 2 GPI), an apoptotic cell-binding protein, were associated with SLE-related autoantibody production. Conclusion Distinct β 2 GPI-reactive T cell responses are associated with SLE-related autoantibodies. Significance Factors enabling β 2 GPI-reactive T cell responses may predispose individuals to SLE.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".