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Record W4410885072 · doi:10.1016/j.immuni.2025.05.004

Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction

2025· article· en· W4410885072 on OpenAlexaff
Patricia S. Grace, Joshua M. Peters, Jaimie Sixsmith, Richard Lu, Edward B. Irvine, Corinne Luedeman, Brooke A. Fenderson, Andrew J. Vickers, Matthew D. Slein, Tanya R. McKitrick, Mohui Wei, Richard D. Cummings, Aaron S. Wallace, Lisa A. Cavacini, Alok Choudhary, Megan K. Proulx, Christopher Sundling, Gunilla Källenius, Rajko Reljić, J. Ernst, Arturo Casadevall, Camille Locht, Abraham Pinter, Christopher M. Sassetti, Bryan D. Bryson, Sarah M. Fortune, Galit Alter

Bibliographic record

VenueImmunity · 2025
Typearticle
Languageen
FieldMedicine
TopicTuberculosis Research and Epidemiology
Canadian institutionsInstitute of Infection and Immunity
FundersOffice of Extramural Research, National Institutes of HealthNational Institutes of HealthRagon Institute of MGH, MIT and HarvardMassachusetts Institute of TechnologyDana-Farber Cancer InstituteNational Institute of Allergy and Infectious DiseasesBill and Melinda Gates Foundation
KeywordsBiologyAntibodyMycobacterium tuberculosisTuberculosisVirologyMicrobiologyMycobacteriumImmunologyBacteriaGeneticsMedicinePathology

Abstract

fetched live from OpenAlex

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), a leading cause of death by an infectious disease globally, has no efficacious vaccine. Antibodies are implicated in M. tuberculosis control, but the mechanisms of action remain poorly understood. We assembled a library of monoclonal antibodies (mAb) and screened for M. tuberculosis-restrictive activity in mice, identifying protective antibodies targeting diverse antigens. To dissect the mechanism of mAb-mediated M. tuberculosis restriction, we optimized a protective lipoarabinomannan-specific mAb, generating Fc variants. In vivo analysis of these Fc variants revealed a role for Fc-effector function in M. tuberculosis restriction. Restrictive Fc variants altered distribution of M. tuberculosis across innate immune cells. Single-cell transcriptomics highlighted distinctly activated pathways within innate immune cell subpopulations, identifying early activation of neutrophils as a key signature of mAb-mediated M. tuberculosis restriction. Therefore, antibody-mediated restriction of M. tuberculosis is associated with reorganization of the tissue-level immune response to infection and depends on the collaboration of antibody Fab and Fc.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.538
Threshold uncertainty score0.462

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
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)0.0000.000

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 head0.016
GPT teacher head0.345
Teacher spread0.329 · 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 teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations12
Published2025
Admission routes1
Has abstractyes

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