Summary for 8DNT
| Entry DOI | 10.2210/pdb8dnt/pdb |
| Descriptor | T-cell receptor alpha chain, T-cell receptor beta chain, Nucleoprotein, ... (5 entities in total) |
| Functional Keywords | tcr complex, mhc, hla, sars-cov-2, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 20 |
| Total formula weight | 379023.57 |
| Authors | Gallagher, D.T.,Wu, D.,Gowthaman, R.,Pierce, B.G.,Mariuzza, R.A.,Weng, N.P. (deposition date: 2022-07-11, release date: 2023-07-19, Last modification date: 2024-10-30) |
| Primary citation | Choy, C.,Chen, J.,Li, J.,Gallagher, D.T.,Lu, J.,Wu, D.,Zou, A.,Hemani, H.,Baptiste, B.A.,Wichmann, E.,Yang, Q.,Ciffelo, J.,Yin, R.,McKelvy, J.,Melvin, D.,Wallace, T.,Dunn, C.,Nguyen, C.,Chia, C.W.,Fan, J.,Ruffolo, J.,Zukley, L.,Shi, G.,Amano, T.,An, Y.,Meirelles, O.,Wu, W.W.,Chou, C.K.,Shen, R.F.,Willis, R.A.,Ko, M.S.H.,Liu, Y.T.,De, S.,Pierce, B.G.,Ferrucci, L.,Egan, J.,Mariuzza, R.,Weng, N.P. SARS-CoV-2 infection establishes a stable and age-independent CD8 + T cell response against a dominant nucleocapsid epitope using restricted T cell receptors. Nat Commun, 14:6725-6725, 2023 Cited by PubMed Abstract: 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 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 Vα gene usage (TRAV12-2) with limited CDR3α 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. PubMed: 37872153DOI: 10.1038/s41467-023-42430-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.18 Å) |
Structure validation
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