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

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TCR sequencing paired with massively parallel 3' RNA-seq reveals clonotypic T cell signatures.
Nature Immunology ( IF 27.7 ) Pub Date : 2019-11-19 , DOI: 10.1038/s41590-019-0544-5
Ang A Tu _{1,

2} , Todd M Gierahn ₁ , Brinda Monian _{1,

3} , Duncan M Morgan _{1,

3} , Naveen K Mehta _{1,

2} , Bert Ruiter _{4,

5} , Wayne G Shreffler _{4,

5,

6} , Alex K Shalek _{1,

7,

8,

9} , J Christopher Love _{1,

3,

8,

9}

Affiliation

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.

中文翻译：

与大规模平行 3' RNA-seq 配对的 TCR 测序揭示了克隆型 T 细胞特征。

高通量 3' 单细胞 RNA 测序 (scRNA-seq) 可以对组织中的单个免疫细胞进行经济高效的详细表征。然而，目前的技术在阐明基本免疫细胞特征的能力方面受到限制，包括赋予抗原特异性的 T 细胞抗原受体 (TCR) 的可变序列。在这里，我们提出了一种策略，可以同时分析来自 3' 条形码 scRNA-seq 样本的 TCR 序列和相应的完整转录组。这种方法与常见的 3' scRNA-seq 方法兼容，并且适用于事后处理的样本。我们应用该技术来识别与免疫小鼠和食物过敏患者共享共同 TCR 的 T 细胞相关的转录特征。我们观察到扩展克隆型亚群中的优先表型，包括与食物过敏相关的 2 型辅助 CD4+ T 细胞 (TH2) 状态。这些结果证明了我们的方法在研究克隆型驱动反应对于理解潜在生物学至关重要的疾病时的实用性。

更新日期：2019-11-20

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