ArticleNature biotechnology2020
Massively parallel interrogation and mining of natively paired human TCRαβ repertoires.
Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- TcrDesign: de novo design of epitope-specific full-length T cell receptors.Science China. Life sciences · 2026Article
- The T Cell Receptor: Molecular Sensor, Therapeutic Mediator and Probabilistic Driver of Adaptive Immunity.Immunological reviews · 2026Review
- Modeling TCR-Epitope Recognition Specificity: What We Should Learn to Succeed.Immunological reviews · 2026Review
- Article
- Structural quality-tier assessment for TCR-pMHC functional enrichment.Frontiers in immunology · 2026Article
- TIRTL-seq: deep, quantitative and affordable paired TCR repertoire sequencing.Nature methods · 2026Article
- Harnessing TCR repertoires: predictive insights and therapeutic monitoring in cancer immunotherapy.Immuno-oncology technology · 2025Review
- Identification of antigen-specific functional CD8iScience · 2025Article
- Long-persisting SARS-CoV-2 spike-specific CD4Nature communications · 2025Article
- Review
- Discovery of tumor-reactive T cell receptors by massively parallel library synthesis and screening.Nature biotechnology · 2025Article
- Targeting cancer with precision: strategical insights into TCR-engineered T cell therapies.Theranostics · 2025Review
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer throughOncology research · 2024Article
- Advancements in mammalian display technology for therapeutic antibody development and beyond: current landscape, challenges, and future prospects.Frontiers in immunology · 2024Review
- High-fidelity large-diversity monoclonal mammalian cell libraries by cell cycle arrested recombinase-mediated cassette exchange.Nucleic acids research · 2023Article
- Cell activation-based screening of natively paired human T cell receptor repertoires.Scientific reports · 2023Article
- Rapid generation of genetically engineered T cells for the treatment of virus-related cancers.Cancer science · 2022Article
- Stitchr: stitching coding TCR nucleotide sequences from V/J/CDR3 information.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
T cells engineered to express antigen-specific T cell receptors (TCRs) are potent therapies for viral infections and cancer. However, efficient identification of clinical candidate TCRs is complicated by the size and complexity of T cell repertoires and the challenges of working with primary T cells. Here we present a high-throughput method to identify TCRs with high functional avidity from diverse human T cell repertoires. The approach used massively parallel microfluidics to generate libraries of natively paired, full-length TCRαβ clones, from millions of primary T cells, which were then expressed in Jurkat cells. The TCRαβ-Jurkat libraries enabled repeated screening and panning for antigen-reactive TCRs using peptide major histocompatibility complex binding and cellular activation. We captured more than 2.9 million natively paired TCRαβ clonotypes from six healthy human donors and identified rare (<0.001% frequency) viral-antigen-reactive TCRs. We also mined a tumor-infiltrating lymphocyte sample from a patient with melanoma and identified several tumor-specific TCRs, which, after expression in primary T cells, led to tumor cell killing.
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Registered trials
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.