Evidence map›Paper›PMID 41610844›Full record

ArticleImmunity2026

Scalable TCR synthesis and screening enable antigen reactivity mapping in vitiligo.

Stephanie A Gaglione, Rachit S Mukkamala, Chirag Krishna, Blake E Smith, Marc H Wadsworth, Scott A Jelinsky, Caleb R Perez, Laura Schmidt-Hong, Erica L Katz, Kyle J Gellatly and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

26 authors.

Stephanie A GaglioneDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Koch Institute for Integrative Cancer Research, Cambridge, MA, USA.
Rachit S MukkamalaKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Chirag KrishnaInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Blake E SmithKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
Marc H WadsworthInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Scott A JelinskyInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Caleb R PerezKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Laura Schmidt-HongDepartment of Immunology, Harvard Medical School, Boston, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
Erica L KatzDepartment of Dermatology, University of Massachusetts Chan Medical School, 364 Plantation St, Worcester, MA, USA.
Kyle J GellatlyProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Lestat R AliDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Jiao ShenDepartment of Immunology, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
Patrick V HolecFletcher Biosciences, Inc., Cambridge, MA, USA.
Qingyang Henry ZhaoKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Amanda O ChanKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ellen J K XuKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Kellie M KravarikInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Julia A GuzovaInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Connor S DobsonKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Harshabad SinghDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Manuel GarberProgram in Bioinformatics and Integrative Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Michael DouganDepartment of Medicine, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Stephanie K DouganDepartment of Immunology, Harvard Medical School, Boston, MA, USA; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
John E HarrisDepartment of Dermatology, University of Massachusetts Chan Medical School, 364 Plantation St, Worcester, MA, USA.
Aaron WinklerInflammation & Immunology Research Unit, Pfizer Inc., Cambridge, MA 02139, USA.
Michael E BirnbaumKoch Institute for Integrative Cancer Research, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: mbirnb@mit.edu.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
P50-Admin Core-Harris/GarbP50AR080593 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI John E Harris · 2022 to 2026
$9.2M
MATCHMAKERS - Creating and training AI tools for TCR binding prediction and designOT2CA297463 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Michael Birnbaum · 2024 to 2026
$2.6M
Repertoire-scale T cell antigen identification via peptide-MHC lentivirus displayDP2AI158126 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BIRNBAUM, MICHAEL · 2020 to 2020
$2.3M
Training in the Molecular Basis of Autoimmunity and AutoinflammationT32AI132152 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Katherine A. Fitzgerald, Ann Marshak-Rothstein · 2018 to 2026
$1.6M
NCI NIH HHS OT2 CA297463NCI NIH HHS P30 CA014051NIAID NIH HHS DP2 AI158126NIAID NIH HHS T32 AI132152NIAMS NIH HHS P50 AR080593NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

T cells initiate targeted immune responses using T cell receptors (TCRs) to recognize specific antigens. Mapping TCRs to antigens at scale remains a major challenge. Here, we developed an approach to synthesize and functionally screen tens of thousands of TCRs simultaneously. TCR rapid assembly for functional testing (TCRAFT) uses a modular strategy to rapidly and inexpensively construct large pools of TCRs from sequences while maintaining TCRα/β pairing. We applied TCRAFT to reconstruct over 3,800 TCRs from vitiligo blister fluid and mapped these TCRs to specific peptide-major histocompatibility complexes using RAPTR, an activation-based library-on-library screening approach. Vitiligo antigen-specific T cells displayed pronounced clonal expansion and transcriptomic signatures similar to antigen-specific T cells in melanoma, pointing to shared features of disease-relevant T cells in autoimmunity and cancer. Demonstrating scalability, we synthesized and screened over 30,800 TCRs from donors with pancreatic ductal adenocarcinoma to capture antigen-reactive TCRs. Our approach expands the scale and accessibility of TCR-antigen screening, which is critical to understanding immunity and developing new immunotherapies.

Indexed as

Epitope MappingReceptors, Antigen, T-CellT-LymphocytesVitiligoHumansReceptors, Antigen, T-Cellantigen recognitionautoimmunityhigh-throughput functional screeningpeptide MHCT cell receptorTCR specificityviral displayvitiligo

Identifiers

PMID41610844
PMCPMC12885239

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Registered trials

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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.