科學家實現T細胞識別程序的精細設計
作者：
小柯機器人發布時間：2020/11/29 22:05:00
美國加州大學舊金山分校Wendell A. Lim小組實現T細胞識別程序的精細設計。相關論文發表在2020年11月27日出版的《科學》雜誌上。
通過使用合成的Notch受體在轉錄上互連多個分子識別事件，研究人員設計了一個多元化的多受體細胞-細胞識別迴路庫。這些合成迴路能夠工程化的T細胞整合細胞外和細胞內抗原識別，對異質性具有魯棒性，並通過整合多達三種具有陽性或陰性邏輯的抗原來實現精確識別。
由三個順序連接的受體組成的三抗原「與」門在體內顯示出選擇性，清除了三抗原腫瘤，同時忽略了相關的二抗原腫瘤。合成迴路中的多個分子識別事件為設計細胞水平識別提供了一種有力的方法。
據介紹，活細胞通常通過整合來自多個受體的信息來識別其正確的伴侶或靶細胞，從而獲得難以通過單個分子相互作用的識別水平。
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
Science：《科學》，創刊於1880年。隸屬於美國科學促進會，最新IF：41.037