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

Autor: Tu AA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA., Gierahn TM; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA., Monian B; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.; Department of Chemical Engineering, MIT, Cambridge, MA, USA., Morgan DM; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.; Department of Chemical Engineering, MIT, Cambridge, MA, USA., Mehta NK; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA.; Department of Biological Engineering, MIT, Cambridge, MA, USA., Ruiter B; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Shreffler WG; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA.; Food Allergy Center, Massachusetts General Hospital, Boston, MA, USA., Shalek AK; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. shalek@mit.edu.; Institute for Medical Engineering & Science and Department of Chemistry, MIT, Cambridge, MA, USA. shalek@mit.edu.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. shalek@mit.edu.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. shalek@mit.edu., Love JC; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA, USA. clove@mit.edu.; Department of Chemical Engineering, MIT, Cambridge, MA, USA. clove@mit.edu.; Broad Institute of MIT and Harvard, Cambridge, MA, USA. clove@mit.edu.; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. clove@mit.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2019 Dec; Vol. 20 (12), pp. 1692-1699. Date of Electronic Publication: 2019 Nov 19.
DOI: 10.1038/s41590-019-0544-5
Abstrakt: 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.
Databáze: MEDLINE
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