ArticleEBioMedicine2020
Ultra-efficient sequencing of T Cell receptor repertoires reveals shared responses in muscle from patients with Myositis.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- T cell immunomonitoring: a comparative analysis of traditional and novel methods to quantify and characterize human antigen-specific T cells.Nature protocols · 2026Review
- Mutant KRAS vaccine with dual checkpoint blockade in resected pancreatic cancer: a phase I trial.Nature communications · 2026Article
- NeoTCRseek: an integrated platform for high-sensitivity identification of neoantigen-specific TCR clonotypes to track clinical T-cell dynamics.Frontiers in immunology · 2026Article
- Characterizing local antibody responses in the muscle of inclusion body myositis patients.Journal of autoimmunity · 2025Article
- Precise identification and tracking of HMGCR-reactive CD4+ T cells in the target tissue of patients with anti-HMGCR immune-mediated necrotising myopathy.Annals of the rheumatic diseases · 2025Article
- Deep exploration of the TCR CDR3β repertoire specific for viral CD4 T-cell epitopes inside the circulating T-cell repertoire.Frontiers in immunology · 2025Article
- Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.Nature immunology · 2024Article
- FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA.Cancer research · 2024Article
- Severe acute myositis and myocarditis on initiation of 6-weekly pembrolizumab post-COVID-19 mRNA vaccination.Journal for immunotherapy of cancer · 2024Article
- The self-reactive FVIII T cell repertoire in healthy individuals relies on a short set of epitopes and public clonotypes.Frontiers in immunology · 2024Article
- Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade.bioRxiv : the preprint server for biology · 2023Article
- Barcoding intracellular reverse transcription enables high-throughput phenotype-coupled T cell receptor analyses.Cell reports methods · 2023Article
- A Narrative Review of Acthar Gel for the Treatment of Myositis.Rheumatology and therapy · 2023Review
- Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type.Aging and disease · 2022Article
- Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis.Science translational medicine · 2022Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMyositis, or idiopathic inflammatory myopathy (IIM), is a group disorders of unknown etiology characterized by the inflammation of skeletal muscle. The role of T cells and their antigenic targets in IIM initiation and progression is poorly understood. T cell receptor (TCR) repertoire sequencing is a powerful approach for characterizing complex T cell responses. However, current TCR sequencing methodologies are complex, expensive, or both, greatly limiting the scale of feasible studies.
methodsHere we present Framework Region 3 AmplifiKation sequencing ("FR3AK-seq"), a simplified multiplex PCR-based approach for the ultra-efficient and quantitative analysis of TCR complementarity determining region 3 (CDR3) repertoires. By using minimal primer sets targeting a conserved region immediately upstream of CDR3, undistorted amplicons are analyzed via short read, single-end sequencing. We also introduce the novel algorithm Inferring Sequences via Efficiency Projection and Primer Incorporation ("ISEPPI") for linking CDR3s to their associated variable genes.
findingsWe find that FR3AK-seq is sensitive and quantitative, performing comparably to two different industry standards. FR3AK-seq and ISEPPI were used to efficiently and inexpensively characterize the T cell infiltrates of surgical muscle biopsies obtained from 145 patients with IIM and controls. A cluster of closely related TCRs was identified in samples from patients with sporadic inclusion body myositis (IBM).
interpretationThe ease and minimal cost of FR3AK-seq removes critical barriers to routine, large-scale TCR CDR3 repertoire analyses, thereby democratizing the quantitative assessment of human TCR repertoires in disease-relevant target tissues. Importantly, discovery of closely related TCRs in muscle from patients with IBM provides evidence for a shared antigen-driven T cell response in this disease of unknown pathogenesis.
fundingThis work was supported by NIH grant U24AI118633 and a Prostate Cancer Foundation Young Investigator Award.
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