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 (TH2) 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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Tu AA,Gierahn TM,Monian B,Morgan DM,Mehta NK,Ruiter B,Shreffler WG,Shalek AK,Love JC

doi

10.1038/s41590-019-0544-5

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

1692-1699

issue

12

eissn

1529-2908

issn

1529-2916

pii

10.1038/s41590-019-0544-5

journal_volume

20

pub_type

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