The historical postulate: Is it the basis, at the level of the system, for self‐nonself discrimination?
Bibliographic record
Abstract
Burnet envisaged the early presence of self-antigens in development, or 'the history' of an animal, ablates the animal's ability to immunologically respond against them. Lederberg added the idea that the continuous presence of self-antigens is required to maintain tolerance throughout life. We refer to Lederberg's proposal as 'The Historical Postulate'. The mechanism of central tolerance, as now understood, is consistent with The Historical Postulate. Some observations, reflecting peripheral tolerance, appear inconsistent with this postulate. For example, some foreign peripheral tissues, grafted onto an animal before the immune system develops, can be rejected as the immune system matures. The original two-signal model of lymphocyte activation was proposed in part because it accounted for peripheral tolerance in a manner consistent with The Historical Postulate. We proposed that lymphocyte activation required antigen-mediated lymphocyte cooperation, whereas antigen would inactivate lymphocytes when insufficient in number to achieve activation. We argue here that the exceptions to The Historical Postulate can be explained by the two-signal model of lymphocyte activation: they reflect the existence of greater numbers of lymphocytes specific for these antigens than for natural peripheral antigens, and so are outside the physiological limits important in selecting through evolution this mechanism of peripheral tolerance. We argue that a consideration of whether The Historical Postulate is valid is important, even if only valid within certain understandable limits. The currently popular DAMP model of CD4 T cell activation is, strictly speaking and in a manner we discuss, in violation of this postulate.
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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 | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.002 | 0.023 |
| Scholarly communication | 0.004 | 0.017 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.003 | 0.006 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".