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Tumor-associated antigen MUC1 contains self epitopes subject to self-tolerance and tumor-associated “foreign” epitopes that elicit effective immunity: important distinction for cancer vaccines (41.60)

2009· article· en· W39549056 on OpenAlexaff
Sean O. Ryan, Michael S. Turner, Leigh Revers, Jean Gariépy, Olivera J. Finn

Bibliographic record

VenueThe Journal of Immunology · 2009
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGlycosylation and Glycoproteins Research
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsEpitopeGlycopeptideAntigenMUC1BiologyImmune toleranceImmunologyImmune systemMicrobiology

Abstract

fetched live from OpenAlex

Abstract Human adenocarcinomas express tumor-associated antigen (TAA) MUC1 that presents to the immune system peptide epitopes as well as glycopeptide epitopes carrying tumor specific carbohydrates. In MUC1-Tg mice responses to MUC1-peptides are suppressed while vaccination with tumor-associated glycopeptides results in effective anti-MUC1 immunity. Transgene negative mice respond equally to both antigens. Using our newly generated TCR transgenic mice with peptide and glycopeptide specific TCRs, we show for the first time that peptide specific CD4 T cells transferred to MUC1-Tg mice are suppressed through mechanisms of peripheral tolerance that are not induced against MUC1-glycopeptide specific CD4 T cells. This tolerance is due to MUC1-peptide epitope presentation in the periphery of healthy MUC1-Tg mice, previously thought to occur primarily in tumor bearing mice. MUC1 glycopeptide epitopes are tumor specific and thus treated as foreign in MUC1-Tg mice, resulting in effective activation of CD4 T cells. Furthermore, glycopeptide-specific T cells provide help to enhance peptide-specific T cell responses. We conclude that TAA contain epitopes that are subject to self tolerance and also tumor specific (foreign) epitopes not affected by self tolerance. It is important to maintain this distinction in attempts to develop effective and safe cancer vaccines. (Supported by NIH T32CA82084, RO1CA56103, CBCRA/CCS)

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.009
GPT teacher head0.271
Teacher spread0.262 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2009
Admission routes1
Has abstractyes

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