Dobson, ConnorReich, AnnaGaglione, StephanieSmith, BlakeKim, EllenDong, JiayiRonsard, LaranceOkonkwo, VintusLingwood, DanielDougan, MichaelDougan, StephanieBrinbaum, Michael2023-09-052022-04Dobson, Connor, Anna Reich, Stephanie Gaglione, Blake Smith, Ellen Kim, Jiayi Dong, Larance Ronsard et al. "Antigen identification and high-throughput interaction mapping by reprogramming viral entry." Nat Methods 19, no. 4 (2022): 449-460. DOI: 10.1038/s41592-022-01436-z1548-70911548-7105https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37376980Deciphering immune recognition is critical to understanding a broad range of diseases, and to develop effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of the adaptive immune repertoire 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.en-USCell BiologyMolecular BiologyBiochemistryBiotechnologyJournal Article2023-09-0510.1038/s41592-022-01436-z