SARS-CoV-2 epitope-specific CD8+ clonotypes persist 8 month post-infection despite reduced clonality.

Abstract

Abstract Memory T cells play a crucial role in acceleration of immune response during reinfection with the same pathogen. Since the beginning of the COVID-19 pandemic, attention has been focused on determining the epitopes of SARS-CoV-2 that give rise to long-lived memory T cells. We examined the immune response to 12 immunogenic CD8+ epitopes in 26 COVID-19 convalescent patients. Paired blood samples were collected shortly after infection and approximately 8 months after. Using ex vivo T cell expansions with a subsequent MHC-tetramer+ cell-sorting and T cell receptor beta-chain (TCRβ) sequencing we studied the epitope-specific CD8+ response on the clonal level. In total in both time points we identified 756 epitope-specific TCRβ sequences. Nine epitopes were immunodominant while five immunogenic epitopes (YLQ, KCY, LLY, KTF and ALW) yielded response in 100% of tested individuals. This coincided with a high number of clones per individual specific to these epitopes (median = 16.5). Despite the very low frequency of specific cells in the total repertoire most (75.4%) of responses were retained at 8-month post-infection. The median number of clones for the top five most immunogenic epitopes dropped to 6. The TCRβ repertoires of T cells specific to the studied epitopes were characterized by different degrees of CDR3 homology. LLY and YLQ-specific TCRβ had the highest degree of mutual similarity while KCY and KTF-specific TCRβ were the most diverse. Our data demonstrates that despite the overall decrease of T cell reactivity and clonality most epitopes are still recognized due to the ability of memory SARS-CoV-2-specific CD8+ cells to survive over prolonged periods of time. The work was supported by the Russian Science Foundation grant 20-15-00395.