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Record W4415596721 · doi:10.1101/2025.10.26.684631

Cross-competition shapes CD8+ T cell hierarchies and differentiation after RNA vaccination

2025· preprint· W4415596721 on OpenAlexaff
Mark O. McCarron, Milena Hornburg, Thomas D. Wu, Ann-Jay Tong, Siri Tähtinen, Martine Darwish, Emily Freund, Ying Feng, David Eisel, Camille-Charlotte Balança, Itai Doron, Huan Lan, Sophie M. Lehar, Yoko Oei, Vincent Javinal, Armando Navarro, Yajun Chestnut, Alan Gutierrez, Sara Wichner, Cecile de la Cruz, Benjamin Haley, Craig Blanchette, Mathias Vormehr, Lena M. Kranz, Uğur Şahin, Ira Mellman, Jill Schartner, Lélia Delamarre

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Language
FieldImmunology and Microbiology
TopicT-cell and B-cell Immunology
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsImmunodominancePriming (agriculture)Cytotoxic T cellSubdominantT cellPhenotypeAntigenCellEffector

Abstract

fetched live from OpenAlex

Short Summary Immunodominance is a universal feature of adaptive immunity that constrains T cell expansion, clonal diversity and breadth resulting in a narrowly focused T cell response. While observed across diverse priming settings and vaccine platforms, the influence of immunodominance on T cell phenotype remains unclear. Using an mRNA lipoplex vaccine encoding multiple antigens to study how immunodominance influences CD8+ T cell fate, we found that dominant CD8+ T cell responses alter the magnitude and phenotype of subdominant responses through peptide-MHC-I stability-mediated T cell cross-competition. Dominant CD8+ T cell responses preferentially acquired markers associated with terminal differentiation and cytotoxic function, while sub-dominant responses adopted memory-precursor and stem-like features. Removal of dominant responses allowed increased expansion of sub-dominant T cell responses and adoption of terminally differentiated effector phenotypes. These findings reveal that immunodominance dynamically shapes the magnitude, breadth and differentiation of CD8+ T cell responses and highlights opportunities to fine-tune T cell responses for therapeutic vaccination.

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.007
GPT teacher head0.210
Teacher spread0.203 · 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

Citations3
Published2025
Admission routes1
Has abstractyes

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