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...
Main Authors: | , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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Springer Science and Business Media LLC
2023
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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. |
first_indexed | 2024-09-23T11:01:40Z |
format | Article |
id | mit-1721.1/147767 |
institution | Massachusetts Institute of Technology |
language | English |
last_indexed | 2024-09-23T11:01:40Z |
publishDate | 2023 |
publisher | Springer Science and Business Media LLC |
record_format | dspace |
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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