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 cells.
“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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Advancing Food Allergy Through Omics Sciences
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- 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
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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