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科学家实现T细胞识别程序的精细设计
作者:小柯机器人 发布时间:2020/11/29 22:05:00

美国加州大学旧金山分校Wendell A. Lim小组实现T细胞识别程序的精细设计。相关论文发表在2020年11月27日出版的《科学》杂志上。

通过使用合成的Notch受体在转录上互连多个分子识别事件,研究人员设计了一个多元化的多受体细胞-细胞识别回路库。这些合成回路能够工程化的T细胞整合细胞外和细胞内抗原识别,对异质性具有鲁棒性,并通过整合多达三种具有阳性或阴性逻辑的抗原来实现精确识别。
 
由三个顺序连接的受体组成的三抗原“与”门在体内显示出选择性,清除了三抗原肿瘤,同时忽略了相关的二抗原肿瘤。合成回路中的多个分子识别事件为设计细胞水平识别提供了一种有力的方法。
 
据介绍,活细胞通常通过整合来自多个受体的信息来识别其正确的伴侣或靶细胞,从而获得难以通过单个分子相互作用的识别水平。
 
附:英文原文

Title: Precise T cell recognition programs designed by transcriptionally linking multiple receptors

Author: Jasper Z. Williams, Greg M. Allen, Devan Shah, Igal S. Sterin, Ki H. Kim, Vivian P. Garcia, Gavin E. Shavey, Wei Yu, Cristina Puig-Saus, Jennifer Tsoi, Antoni Ribas, Kole T. Roybal, Wendell A. Lim

Issue&Volume: 2020/11/27

Abstract: Living cells often identify their correct partner or target cells by integrating information from multiple receptors, achieving levels of recognition that are difficult to obtain with individual molecular interactions. In this study, we engineered a diverse library of multireceptor cell-cell recognition circuits by using synthetic Notch receptors to transcriptionally interconnect multiple molecular recognition events. These synthetic circuits allow engineered T cells to integrate extra- and intracellular antigen recognition, are robust to heterogeneity, and achieve precise recognition by integrating up to three different antigens with positive or negative logic. A three-antigen AND gate composed of three sequentially linked receptors shows selectivity in vivo, clearing three-antigen tumors while ignoring related two-antigen tumors. Daisy-chaining multiple molecular recognition events together in synthetic circuits provides a powerful way to engineer cellular-level recognition.

DOI: 10.1126/science.abc6270

Source: https://science.sciencemag.org/content/370/6520/1099

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037