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

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 a...

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Main Authors: 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
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2023
Online Access:https://hdl.handle.net/1721.1/147767
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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
author2 Massachusetts Institute of Technology. Department of Biological Engineering
author_facet Massachusetts Institute of Technology. Department of Biological Engineering
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
author_sort Dobson, Connor S
collection MIT
description 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.
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spelling mit-1721.1/1477672023-01-28T03:33:47Z Antigen identification and high-throughput interaction mapping by reprogramming viral entry 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 Massachusetts Institute of Technology. Department of Biological Engineering 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. 2023-01-27T19:43:38Z 2023-01-27T19:43:38Z 2022 2023-01-27T19:11:36Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/147767 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). en 10.1038/S41592-022-01436-Z Nature Methods Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC PMC
spellingShingle 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
Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title_full Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title_fullStr Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title_full_unstemmed Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title_short Antigen identification and high-throughput interaction mapping by reprogramming viral entry
title_sort antigen identification and high throughput interaction mapping by reprogramming viral entry
url https://hdl.handle.net/1721.1/147767
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