8dnt

Publication Abstract from PubMed

The resolution of SARS-CoV-2 replication hinges on cell-mediated immunity, wherein CD8(+) T cells play a vital role. Nonetheless, the characterization of the specificity and TCR composition of CD8(+) T cells targeting non-spike protein of SARS-CoV-2 before and after infection remains incomplete. Here, we analyzed CD8(+) T cells recognizing six epitopes from the SARS-CoV-2 nucleocapsid (N) protein and found that SARS-CoV-2 infection slightly increased the frequencies of N-recognizing CD8(+) T cells but significantly enhanced activation-induced proliferation compared to that of the uninfected donors. The frequencies of N-specific CD8(+) T cells and their proliferative response to stimulation did not decrease over one year. We identified the N(222-230) peptide (LLLDRLNQL, referred to as LLL thereafter) as a dominant epitope that elicited the greatest proliferative response from both convalescent and uninfected donors. Single-cell sequencing of T cell receptors (TCR) from LLL-specific CD8(+) T cells revealed highly restricted Valpha gene usage (TRAV12-2) with limited CDR3alpha motifs, supported by structural characterization of the TCR-LLL-HLA-A2 complex. Lastly, transcriptome analysis of LLL-specific CD8(+) T cells from donors who had expansion (expanders) or no expansion (non-expanders) after in vitro stimulation identified increased chromatin modification and innate immune functions of CD8(+) T cells in non-expanders. These results suggests that SARS-CoV-2 infection induces LLL-specific CD8(+) T cell responses with a restricted TCR repertoire.

SARS-CoV-2 infection establishes a stable and age-independent CD8(+) T cell response against a dominant nucleocapsid epitope using restricted T cell receptors.,Choy C, Chen J, Li J, Gallagher DT, Lu J, Wu D, Zou A, Hemani H, Baptiste BA, Wichmann E, Yang Q, Ciffelo J, Yin R, McKelvy J, Melvin D, Wallace T, Dunn C, Nguyen C, Chia CW, Fan J, Ruffolo J, Zukley L, Shi G, Amano T, An Y, Meirelles O, Wu WW, Chou CK, Shen RF, Willis RA, Ko MSH, Liu YT, De S, Pierce BG, Ferrucci L, Egan J, Mariuzza R, Weng NP Nat Commun. 2023 Oct 23;14(1):6725. doi: 10.1038/s41467-023-42430-z. PMID:37872153^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.