Good news! Very clever approach!
"... MIT biological engineers have now devised an experimental tool that allows them to precisely pick out interactions between a particular immune cell and its target antigen. The new technique, which uses engineered viruses to present many different antigens to huge populations of immune cells, could allow large-scale screens of such interactions. ...
To demonstrate the accuracy of their technique, the researchers created a pool of viruses with antigens from 100 different viruses, including influenza, cytomegalovirus, and Epstein-Barr virus. They screened these viruses against about 400,000 T cells and showed that the technique could correctly pick out antigen-T-cell receptor pairings that had been previously identified. ..."
To create a simple way to screen so many possible interactions, the researchers engineered a specialized form of a lentivirus, a type of virus that scientists often use to deliver genes because it can integrate pieces of DNA into host cells. These viruses have an envelope protein called VSV-G that can bind to receptors on the surface of many types of human cells, including immune cells, and infect them.
For this study, the researchers modified the VSV-G protein so that it cannot infect a cell on its own, instead relying on an antigen of the researchers’ choosing. This modified version of VSV-G can only help the lentivirus get into a cell if the paired antigen binds to a human B or T-cell receptor that recognizes the antigen.
Once the virus enters, it integrates itself into the host cell’s genome. Therefore, by sequencing the genome of all the cells in the sample, the researchers can discover both the antigen expressed by the virus that infected the cell and the sequence of the T or B-cell receptor that allowed it to enter. ...To demonstrate the accuracy of their technique, the researchers created a pool of viruses with antigens from 100 different viruses, including influenza, cytomegalovirus, and Epstein-Barr virus. They screened these viruses against about 400,000 T cells and showed that the technique could correctly pick out antigen-T-cell receptor pairings that had been previously identified. ..."
From the 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."
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