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新方法实现抗原识别和高通量相互作用图谱的绘制
2022-04-14 16:37

美国麻省理工学院Michael E. Birnbaum研究小组通过重编程病毒的进入实现抗原识别和高通量相互作用图谱的绘制。相关论文于2022年4月8日在线发表在《自然—方法学》杂志上。

研究人员表示,破解免疫识别对于理解广泛的疾病以及开发有效的疫苗和免疫疗法至关重要。由于缺乏能够同时捕捉适应性免疫受体复合物的复杂性和潜在抗原的技术,这方面的努力受到限制。

为了解决这个问题,研究人员提出了靶向逆转录病毒的受体-抗原配对,它结合了病毒假分型和分子工程方法,通过在慢病毒表面显示抗原并在病毒基因组中编码它们的身份来实现一锅式库对库的互动筛选。对表达人类T或B细胞受体的细胞系进行抗原特异性病毒感染,可以通过单细胞测序读出抗原和受体的身份。由此产生的系统是模块化的、可扩展的,与任何细胞类型兼容。这些技术为有针对性的病毒进入、分子工程和相互作用筛选提供了一套工具,并具有广泛的应用潜力。

附:英文原文

Title: Antigen identification and high-throughput interaction mapping by reprogramming viral entry

Author: Dobson, Connor S., Reich, Anna N., Gaglione, Stephanie, Smith, Blake E., Kim, Ellen J., Dong, Jiayi, Ronsard, Larance, Okonkwo, Vintus, Lingwood, Daniel, Dougan, Michael, Dougan, Stephanie K., Birnbaum, Michael E.

Issue&Volume: 2022-04-08

Abstract: Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immunoreceptor repertoires and the landscape of potential antigens. To address this, we present receptor–antigen pairing by targeted retroviruses, which combines viral pseudotyping and molecular engineering approaches to enable one-pot library-on-library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cell lines expressing human T or B cell receptors allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable and compatible with any cell type. These techniques provide a suite of tools for targeted viral entry, molecular engineering and interaction screens with broad potential applications.

DOI: 10.1038/s41592-022-01436-z

Source: https://www.nature.com/articles/s41592-022-01436-z

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:47.99
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex


本期文章:《自然—方法学》:Online/在线发表

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