科學家繪製出T細胞受體庫的功能圖譜
作者：
小柯機器人發布時間：2021/1/8 16:23:57
美國德克薩斯大學西南醫學中心Tao Wang課題組通過單T細胞轉錄組學繪製出T細胞受體庫的功能圖譜。相關論文於2021年1月6日在線發表在《自然—方法學》雜誌上。
據研究人員介紹，人們已經開發了許多實驗和生物信息學方法來表徵人類T細胞受體（TCR）庫。但是，TCR譜的未知功能相關性阻礙了對T細胞生物學的無偏認知。
為了解決這一不足，研究人員開發了tessa，該工具可將TCR與T細胞的基因表達整合在一起，來評估TCR對T細胞表型的影響。tessa利用了將單細胞RNA測序與TCR測序相結合的技術。研究人員驗證了tessa，並顯示了其優於現有方法的優越性。
使用tessa，研究人員發現，TCR相似性限制了T細胞的表型相似，並決定了具有趨同TCR T細胞克隆型的抗原靶向效率梯度。研究人員發現，這種限制可以預測免疫治療後T細胞的功能二分法，並且會在腫瘤中減弱。
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