Cited by 131Single-cell and spatial transcriptomicsT-cell and B-cell ImmunologyMonoclonal and Polyclonal Antibodies Research

TCR sequencing paired with massively parallel 3′ RNA-seq reveals clonotypic T cell signatures

Tu, Ang A., Gierahn, Todd M., Monian, Brinda, Morgan, Duncan M., Mehta, Naveen K., Ruiter, Bert, Shreffler, Wayne G., Shalek, Alex K. +1 more·2019·Nature Immunology

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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Crossref · 10.1038/s41590-019-0544-5

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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
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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