8DNT

SARS-CoV-2 specific T cell receptor

これはPDB形式変換不可エントリーです。

8DNT の概要

• エントリーDOI: 10.2210/pdb8dnt/pdb
• 分子名称: T-cell receptor alpha chain, T-cell receptor beta chain, Nucleoprotein, ... (5 entities in total)
• 機能のキーワード: tcr complex, mhc, hla, sars-cov-2, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 379023.57

構造登録者

Gallagher, D.T.,Wu, D.,Gowthaman, R.,Pierce, B.G.,Mariuzza, R.A.,Weng, N.P. (登録日: 2022-07-11, 公開日: 2023-07-19, 最終更新日: 2024-10-30)

主引用文献

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

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: 37872153
DOI: 10.1038/s41467-023-42430-z

実験手法

X-RAY DIFFRACTION (3.18 Å)