Indirect Recognition of T-Cell Epitopes Derived from the α3 and Transmembrane Domain of HLA-A2
Bibliographic record
Abstract
Indirect allorecognition has been implicated in the mechanism of chronic rejection and alloantibody formation but precise definition of the epitopes involved has been limited. We have undertaken a detailed assessment of the antigenic properties of peptides derived from HLA-A2. Candidate epitopes were identified in vitro by assessment of MHC class II binding. The immune response to these epitopes was determined in patients awaiting a renal transplant by the assessment of PBMC activation using gamma-interferon ELISPOT. Twenty-two of fifty-five patients responded to peptides from HLA-A2 and this was associated with but not confined to those who had made antibody to HLA-A2 (14/18). Nineteen of twenty-two patients responded to peptides derived from the hypervariable alpha1 and alpha2 domains and 18/22 responded to peptides from the alpha 3 and transmembrane domain, the sequences of which show little polymorphism. In six patients, the sequence of these peptides was identical to self, that is, the response was autoimmune. The finding of indirect epitopes derived from regions of MHC class I that exhibit little polymorphism provides a novel perspective on the immune response to alloantigen and has potential implications for the development of specific therapies.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 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".