Evidence map›Paper›PMID 38956325›Full record

ArticleNature biotechnology2025

High-throughput discovery of MHC class I- and II-restricted T cell epitopes using synthetic cellular circuits.

Ayano C Kohlgruber, Mohammad H Dezfulian, Brandon M Sie, Charlotte I Wang, Tomasz Kula, Uri Laserson, H Benjamin Larman, Stephen J Elledge

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed.

  1. Review
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  4. Ensembles ofbioRxiv : the preprint server for biology · 2026
    Article
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  15. Article
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  18. bioRxiv : the preprint server for biology · 2025
    Article
  19. Computational modeling of human genetic variants in mice.bioRxiv : the preprint server for biology · 2025
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ayano C KohlgruberDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6758-3966
Mohammad H DezfulianDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Brandon M SieDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9405-1850
Charlotte I WangDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Tomasz KulaDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Uri LasersonDepartment of Genetics and Genomic Sciences and Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8429-7686
H Benjamin LarmanInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7863-196X
Stephen J ElledgeDivision of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. selledge@genetics.med.harvard.edu.ORCID http://orcid.org/0000-0001-7923-6283

Funding

Analysis of the Mammalian DNA Damage ResponseR01CA234600 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELLEDGE, STEPHEN J · 2019 to 2023
$2.0M
Decoding synovial CD4+ T cell antigen specificities in Rheumatoid ArthritisR00AR081896 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI Ayano Christine Kohlgruber · 2024 to 2026
$709k
Decoding synovial CD4+ T cell antigen specificities in Rheumatoid ArthritisK99AR081896 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI KOHLGRUBER, AYANO CHRISTINE · 2023 to 2023
$94k
NCI NIH HHS R01 CA234600NIAMS NIH HHS K99 AR081896NIAMS NIH HHS R00 AR081896
6 · The paper itself

Abstract

Antigen discovery technologies have largely focused on major histocompatibility complex (MHC) class I-restricted human T cell receptors (TCRs), leaving methods for MHC class II-restricted and mouse TCR reactivities relatively undeveloped. Here we present TCR mapping of antigenic peptides (TCR-MAP), an antigen discovery method that uses a synthetic TCR-stimulated circuit in immortalized T cells to activate sortase-mediated tagging of engineered antigen-presenting cells (APCs) expressing processed peptides on MHCs. Live, tagged APCs can be directly purified for deconvolution by sequencing, enabling TCRs with unknown specificity to be queried against barcoded peptide libraries in a pooled screening context. TCR-MAP accurately captures self-reactivities or viral reactivities with high throughput and sensitivity for both MHC class I-restricted and class II-restricted TCRs. We elucidate problematic cross-reactivities of clinical TCRs targeting the cancer/testis melanoma-associated antigen A3 and discover targets of myocarditis-inciting autoreactive T cells in mice. TCR-MAP has the potential to accelerate T cell antigen discovery efforts in the context of cancer, infectious disease and autoimmunity.

Indexed as

Epitopes, T-LymphocyteHigh-Throughput Screening AssaysHistocompatibility Antigens Class IHistocompatibility Antigens Class IIAnimalsAntigen-Presenting CellsHumansMicePeptide LibraryReceptors, Antigen, T-CellT-LymphocytesEpitopes, T-LymphocyteHistocompatibility Antigens Class IHistocompatibility Antigens Class IIPeptide LibraryReceptors, Antigen, T-Cell

Identifiers

PMID38956325
PMCPMC11994455

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.