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

Dobson, C. S.; Reich, A. N.; Gaglione, S.; Smith, B. E.; Kim, E. J.; Dong, J.; Ronsard, L.; Okonkwo, V.; Lingwood, D.; Dougan, M.; Dougan, S. K.; Birnbaum, M. E.

doi:10.1101/2021.09.18.460796

bioRxiv · 10.1101/2021.09.18.460796

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

Dobson, C. S.·Reich, A. N.·Gaglione, S.·Smith, B. E.·Kim, E. J.·Dong, J.·Ronsard, L.·Okonkwo, V.·Lingwood, D.·Dougan, M.·Dougan, S. K.·Birnbaum, M. E.

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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 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 cells allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable, and compatible with any cell type, making it easily implemented. 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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Dobson, C. S., Reich, A. N., Gaglione, S., Smith, B. E., Kim, E. J., Dong, J., Ronsard, L., Okonkwo, V., Lingwood, D., Dougan, M., Dougan, S. K., Birnbaum, M. E.. 2021-09-20. Antigen identification and high-throughput interaction mapping by reprogramming viral entry. https://doi.org/10.1101/2021.09.18.460796

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