Background The adaptive immune system identifies foreign antigens based on a series of highly specific interactions involving multiple immune cell types. Identifying the exact mechanisms of said interactions can be difficult to achieve using bulk sequencing methods due to poor resolution. Single cell sequencing offers the ability to match a specific antigen to an immune cell receptor sequence at the cellular level.

Methods We used Barcode Enabled Antigen Mapping (BEAM) and Single Cell Immune Profiling technology to profile hundreds of thousands of human peripheral blood mononuclear cells (PBMCs) from a donor following their recovery from COVID-19. These cells were screened for potential binding interactions with multiple antigens from SARS-CoV-2 and other viral pathogens. Sequencing data were also generated for gene expression and paired sequences for both BCRs and TCRs.

Results The combination of these two techniques allowed us to identify a number of antigen-specific clonotypes of T cells and B cells. The high throughput of the experiment allowed us to gain understanding on a global scale of the state of the immune system following recovery from a COVID-19 infection, as well as to identify potentially rare clonotypes that may not have been discerned from a smaller sample size.

Conclusions This experiment demonstrates the ability of BEAM to both profile the entire immune system at the cellular level at a given point in time as well as distinguish specific antigen-receptor interactions with the same resolution. Insights provided by similar experiments could be invaluable in the creation of precision cell therapies for use in cancer treatment, as well as the development of vaccines and analysis of allergic and autoimmune responses.