Clonal diversity predicts persistence of SARS-CoV-2 epitope-specific T cell response

T cells play a crucial role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. Using ex vivo epitope-specific T cell expansions and Next Generation sequencing we identified 756 clonotypes specific to nine SARS-CoV-2 CD8+ T cell epitopes. Some of them were recognized by highly similar public clonotypes while receptors for other epitopes were extremely diverse. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the some epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.