美国德克萨斯大学西南医学中心Tao Wang课题组通过单T细胞转录组学绘制出T细胞受体库的功能图谱。相关论文于2021年1月6日在线发表在《自然—方法学》杂志上。

据研究人员介绍，人们已经开发了许多实验和生物信息学方法来表征人类T细胞受体（TCR）库。但是，TCR谱的未知功能相关性阻碍了对T细胞生物学的无偏认知。

为了解决这一不足，研究人员开发了tessa，该工具可将TCR与T细胞的基因表达整合在一起，来评估TCR对T细胞表型的影响。tessa利用了将单细胞RNA测序与TCR测序相结合的技术。研究人员验证了tessa，并显示了其优于现有方法的优越性。

使用tessa，研究人员发现，TCR相似性限制了T细胞的表型相似，并决定了具有趋同TCR T细胞克隆型的抗原靶向效率梯度。研究人员发现，这种限制可以预测免疫治疗后T细胞的功能二分法，并且会在肿瘤中减弱。

附：英文原文

Title: Mapping the functional landscape of T cell receptor repertoires by single-T cell transcriptomics

Author: Ze Zhang, Danyi Xiong, Xinlei Wang, Hongyu Liu, Tao Wang

Issue&Volume: 2021-01-06

Abstract: Many experimental and bioinformatics approaches have been developed to characterize the human T cell receptor (TCR) repertoire. However, the unknown functional relevance of TCR profiling hinders unbiased interpretation of the biology of T cells. To address this inadequacy, we developed tessa, a tool to integrate TCRs with gene expression of T cells to estimate the effect that TCRs confer on the phenotypes of T cells. Tessa leveraged techniques combining single-cell RNA-sequencing with TCR sequencing. We validated tessa and showed its superiority over existing approaches that investigate only the TCR sequences. With tessa, we demonstrated that TCR similarity constrains the phenotypes of T cells to be similar and dictates a gradient in antigen targeting efficiency of T cell clonotypes with convergent TCRs. We showed this constraint could predict a functional dichotomization of T cells postimmunotherapy treatment and is weakened in tumor contexts. Tessa, a Bayesian model, integrates TCR sequencing data with gene expression data to analyze the effect of the TCR repertoire on T cell functionality.

DOI: 10.1038/s41592-020-01020-3

Source: https://www.nature.com/articles/s41592-020-01020-3