Tregitope update: Mechanism of action parallels IVIg
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
In the course of screening immunoglobulin G (IgG) sequences for T cell epitopes, we identified novel Treg epitope peptides, now called Tregitopes, contained in the highly conserved framework regions of Fab and Fc. Tregitopes may provide one explanation for the expansion and stimulation of Treg cells following intravenous immunoglobulin (IVIg) therapy. Their distinguishing characteristics include in silico signatures that suggest high-affinity binding to multiple human HLA class II DR and conservation across IgG isotypes and mammalian species with only minor amino acid modifications. Tregitopes induce expansion of CD4(+)/CD25(hi)/FoxP3(+) T cells and suppress immune responses to co-incubated antigens in vitro. By comparing the human IgG Tregitopes (hTregitopes 167 and 289, located in the IgG CH1 and CH2 domains) and Fab to murine sequences, we identified class II-restricted murine Tregitope homologs (mTregitopes). In vivo, mTregitopes suppress inflammation and reproducibly induce Tregs to expand. In vitro studies suggest that the Tregitope mechanism of action is to induce Tregs to respond, leading to production of regulatory signals, followed by modulation of dendritic cell phenotype. The identification of Treg epitopes in IgG suggests that additional Tregitopes may also be present in other autologous proteins; methods for identifying and validating such peptides are described here. The discovery of Tregitopes in IgG and other autologous proteins may lead to the development of new insights as to the role of Tregs in autoimmune diseases.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.015 |
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 it