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Nat Immunol DOI:10.1038/s41590-019-0544-5

TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.

Publication TypeJournal Article
Year of Publication2019
AuthorsTu, AA, Gierahn, TM, Monian, B, Morgan, DM, Mehta, NK, Ruiter, B, Shreffler, WG, Shalek, AK, J Love, C
JournalNat Immunol
Volume20
Issue12
Pages1692-1699
Date Published2019 12
ISSN1529-2916
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 (T2) 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.

DOI10.1038/s41590-019-0544-5
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31745340?dopt=Abstract

Alternate JournalNat. Immunol.
PubMed ID31745340
Grant ListU19AI095261 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
5P01AI039671 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
5U19AI089992 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
U19AI095261 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
5P01AI039671 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
U19AI095261 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
5P01AI039671 / / U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /
1U54CA217377 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
2RM1HG006193 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
1R33CA202820 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
1R01AI138546 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
1R01DA046277 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
1U2CCA23319501 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /