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Record W4308562598 · doi:10.1101/2022.11.08.515436

Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection

2022· preprint· en· W4308562598 on OpenAlexaff
Martina Milighetti, Yanchun Peng, Cedric Tan, Michal Mark, Gayathri Nageswaran, Suzanne Byrne, Tahel Ronel, Andreas Mayer, Aneesh Chandran, Joshua Rosenheim, Matthew V. X. Whelan, Xuan Yao, Guihai Liu, Suet Ling Felce, Tao Dong, Alexander J. Mentzer, Julian C. Knight, François Balloux, Erez Greenstein, Shlomit Reich-Zeliger, Corrina Pade, Joseph M. Gibbons, Amanda Semper, Tim Brooks, Ashley Otter, Daniel M. Altmann, Rosemary J. Boyton, Mala K. Maini, Áine McKnight, Charlotte Manisty, Thomas A. Treibel, James Moon, Mahdad Noursadeghi, Benny Chain

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2022
Typepreprint
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsInstitute of Infection and Immunity
FundersBarts and The London School of Medicine and DentistryMedical Research CouncilNational Institutes of HealthSamsung Biomedical Research InstituteChinese Academy of Medical SciencesUK Coronavirus Immunology ConsortiumUniversity College London Hospitals NHS Foundation TrustRosetrees TrustInstitute for Translational Medicine and TherapeuticsBritish Heart FoundationUniversity College LondonCystic Fibrosis TrustCancer Research UKGW PharmaceuticalsBarts CharityUK Research and InnovationNIHR Oxford Biomedical Research CentreJohn Black Charitable FoundationWellcome TrustNational Institute for Health and Care Research
KeywordsLymphocytic choriomeningitisT-cell receptorBiologyVirologyRepertoireEpitopeT cellImmunityImmunologyCd4 t cellViral infectionVirusImmune systemCD8Antibody

Abstract

fetched live from OpenAlex

Abstract We analyzed the dynamics of the earliest T cell response to SARS-COV-2. A wave of TCRs strongly but transiently expand during infection, frequently peaking the same week as the first positive PCR test. These expanding TCR CDR3s were enriched for sequences functionally annotated as SARS-COV-2 specific. Most epitopes recognized by the expanding TCRs were highly conserved between SARS-COV-2 strains, but not with circulating human coronaviruses. Many expanding CDR3s were also present at high precursor frequency in pre-pandemic TCR repertoires. A similar set of early response TCRs specific for lymphocytic choriomeningitis virus epitopes were also found at high frequency in the pre-infection naïve repertoire. High frequency naïve precursors may allow the T cell response to respond rapidly during the crucial early phases of acute viral infection. One-Sentence Summary High frequency naïve precursors underly the rapid T cell response during the crucial early phases of acute viral infection.

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 score0.005
Threshold uncertainty score0.018

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)0.0050.002

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.

Opus teacher head0.034
GPT teacher head0.307
Teacher spread0.272 · 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
Published2022
Admission routes1
Has abstractyes

Explore more

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