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Resolving SARS-CoV-2 CD4+ T cell specificity via reverse epitope discovery

2022; Elsevier BV; Volume: 3; Issue: 8 Linguagem: Inglês

10.1016/j.xcrm.2022.100697

2666-3791

Mikhail V. Pogorelyy, Elisa Rosati, Anastasia A. Minervina, Robert C. Mettelman, Alexander Scheffold, André Franke, Petra Bächer, Paul G. Thomas,

CAR-T cell therapy research

The current strategy to detect immunodominant T cell responses focuses on the antigen, employing large peptide pools to screen for functional cell activation. However, these approaches are labor and sample intensive and scale poorly with increasing size of the pathogen peptidome. T cell receptors (TCRs) recognizing the same epitope frequently have highly similar sequences, and thus, the presence of large sequence similarity clusters in the TCR repertoire likely identify the most public and immunodominant responses. Here, we perform a meta-analysis of large, publicly available single-cell and bulk TCR datasets from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals to identify public CD4