Antigen identification and high-throughput interaction mapping by reprogramming viral entry
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nihms-1785268.pdf
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Published version
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4.58 MB
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Author(s) • • • • • • • • •
Dobson, Connor S
Reich, Anna N
Gaglione, Stephanie
Smith, Blake E
Kim, Ellen J
Dong, Jiayi
Ronsard, Larance
Okonkwo, Vintus
Lingwood, Daniel
Dougan, Michael
Date Issued
2022
Journal
Nature Methods
Publisher
Springer Science and Business Media LLC
Citation
Dobson, Connor S, Reich, Anna N, Gaglione, Stephanie, Smith, Blake E, Kim, Ellen J et al. 2022. "Antigen identification and high-throughput interaction mapping by reprogramming viral entry." Nature Methods, 19 (4).
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1038/S41592-022-01436-Z