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TCR sequencing paired with massively parallel 3′ RNA-seq reveals clonotypic T cell signatures
Abstract
High-throughput 3' single-cell RNA-sequencing (scRNA-seq) allows cost-effective, detailed characterization of individual immune cells from tissues. Current techniques, however, are limited in their ability to elucidate essential immune cell features, including variable sequences of T cell antigen receptors (TCRs) that confer antigen specificity. Here, we present a strategy that enables simultaneous analysis of TCR sequences and corresponding full transcriptomes from 3'-barcoded scRNA-seq samples. This approach is compatible with common 3' scRNA-seq methods, and adaptable to processed samples post hoc. We applied the technique to identify transcriptional signatures associated with T cells sharing common TCRs from immunized mice and from patients with food allergy. We observed preferential phenotypes among subsets of expanded clonotypes, including type 2 helper CD4+ T cell (T H 2) states associated with food allergy. These results demonstrate the utility of our method when studying diseases in which clonotype-driven responses are critical to understanding the underlying biology.
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“Several methods have been published pairing gene expression with TCR sequences in single cells89–92.”
From The technological landscape and applications of single-cell multi-omics (2023) · cites this paper as [91]
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Metadata
- Authors
- Tu, A. A., Gierahn, T. M., Monian, B., Morgan, D. M., Mehta, N. K., Ruiter, B., Shreffler, W. G., Shalek, A. K., & Love, J. C.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- Harvard University (US)
- Broad Institute (US)
- Corresponding author
- Shalek, Alex K.
- Love, J. Christopher
- ORCID
- Venue
- Nature Immunology
- Published
- 2019-11-19
- Volume
- 20
- Issue
- 12
- Pages
- 1692-1699
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2991527058
- Cited by
- 128
- References
- 63
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 26 · 2023: 21 · 2022: 28 · 2021: 16 · 2020: 15 · 2019: 1
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Broad Institute
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (U19AI095261, 5P01AI039671, 5U19AI089992)
- Koch Institute - Dana-Farber/Harvard Cancer Center Bridge Project.
- U.S. Department of Health & Human Services | National Institutes of Health (1U54CA217377, 2RM1HG006193, 1R33CA202820, 1R01AI138546, 1R01DA046277, 1U2CCA23319501)
- Searle Scholars Program, Beckman Young Investigator Program,Pew-Stewart Scholars Program for Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- T cell receptor, TCR sequencing, single-cell RNA sequencing, T cell transcriptome, Th2 cells, food allergy, immunized mice
- MeSH terms
- Animals, Cells, Cultured, Female, Humans, Immunoglobulin E, Immunization, Male, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, alpha-beta, CD8-Positive T-Lymphocytes, Th2 Cells, Peanut Hypersensitivity, Complementarity Determining Regions, T-Cell Antigen Receptor Specificity, Papillomavirus E7 Proteins, Mice, Antigens, Plant, 2S Albumins, Plant, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Transcriptome
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