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新测序方法揭示克隆型T细胞的特征
作者:小柯机器人 发布时间:2019/11/20 15:13:38

美国麻省理工学院科赫综合癌症研究所J. Christopher Love和Alex K. Shalek研究组合作,利用TCR测序与大规模并行3’RNA-seq揭示了克隆型T细胞特征。 这一研究成果11月19日在线发表在《自然—免疫学》上。

研究人员提出了一种新方法,该方法可以同时分析3'条形码单细胞RNA测序(scRNA-seq)样品中的T细胞抗原受体(TCR)序列和相应的完整转录组。该方法与常见的3'scRNA-seq兼容,并且适用于处理后的样品。

研究人员应用该技术来识别与T细胞相关的转录特征,这些T细胞具有共同的TCR,且这些TCR来自免疫小鼠和食物过敏的患者。

研究人员发现了扩展克隆型子集之间的优势表型,包括与食物过敏相关的2型辅助CD4 + T细胞(TH2)。这些结果证明该方法在研究疾病时的效用,在这种疾病中,克隆型驱动的应答对于理解基础生物学至关重要。

研究人员表示,高通量的3' scRNA-seq可对组织中的单个免疫细胞进行有效且详细表征。然而,当前的技术对阐明免疫细胞的必需功能的能力是有限的,例如揭示赋予抗原特异性TCR的可变序列。

附:英文原文

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

Author: Ang A. Tu, Todd M. Gierahn, Brinda Monian, Duncan M. Morgan, Naveen K. Mehta, Bert Ruiter, Wayne G. Shreffler, Alex K. Shalek, J. Christopher Love

Issue&Volume: 2019-11-19

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.

DOI: 10.1038/s41590-019-0544-5

Source: https://www.nature.com/articles/s41590-019-0544-5

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex