SARS-CoV-2 infection establishes an enhanced, stable, and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using highly restricted TCRs
In vitro antigenic challenge identified N222-230 (LLLDRLNQL referred to as LLL) as a dominant epitope that elicited the greatest response (number of responders and magnitude of expansion) from both convalescent and uninfected donors.  Analysis of scTCRseq of LLL-specific CD8+ T cells using scTCRseq revealed highly restricted V-gene usage (TRAV12-2) with limited CDR3 motifs, which was supported by structural characterization of a TCR–LLL–HLA-A2 complex. Lastly, transcriptome analysis of CD8+ T cells between expanders and non-expanders identified increased gene expressions associated with differentiation of CD8+ T cells from non- expanders which are shared across the different subsets in a TCR-independent manner. These results show that SARS-CoV-2 infection resulted in significantly enhanced proliferation of LLL-specific CD8+ T cells and suggest that an altered transcriptome is the underlying mechanism controlling activation-induced expansion of LLL-specific CD8+ T cells. Overall design: Single Cell sequencing of TCRs and Gene Expression