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

Antigen identification and high-throughput interaction mapping by reprogramming viral entry.
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抗原鉴定和病毒进入重编程的高通量相互作用图谱。

DOI:
10.1038/s41592-022-01436-z
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发表时间:
2022-04
期刊:
影响因子:
48
通讯作者:
Birnbaum, Michael E.
Birnbaum, Michael E.
中科院分区:
生物学1区
文献类型:
--
作者:
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.

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破译免疫识别对于了解广泛的疾病以及开发有效的疫苗和免疫疗法至关重要。这样做的努力受到缺乏能够同时捕捉适应性免疫受体谱系的复杂性和潜在抗原格局的技术的限制。为了解决这个问题,我们提出了RAPTR(靶向逆转录病毒的受体-抗原配对)。RaptR结合了病毒伪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,在库交互屏幕上实现一锅库。抗原特异性病毒感染表达人T或B细胞受体的细胞系,允许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,并与任何单元类型兼容。这些技术为靶向病毒进入、分子工程和相互作用筛选提供了一套新的工具,具有广泛的潜在应用。
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 immune receptor repertoires and the landscape of potential antigens. To address this, we present RAPTR (Receptor-Antigen Pairing by Targeted Retroviruses). RAPTR 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 new tools for targeted viral entry, molecular engineering, and interaction screens with broad potential applications.
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