8YE4

The complex of TCR NYN-I and HLA-A24 bound to SARS-CoV-2 Spike448-456 peptide NYNYLYRLF

8YE4 の概要

• エントリーDOI: 10.2210/pdb8ye4/pdb
• 分子名称: MHC class I antigen precusor, Beta-2-microglobulin, Spike protein S1, ... (6 entities in total)
• 機能のキーワード: sars-cov-2, tcr-pmhc complex, cd8 t cell epitope, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 184240.36

構造登録者

Deng, S.S.,Jin, T.C.,Xu, Z.H.,Wang, M.H. (登録日: 2024-02-21, 公開日: 2024-08-21, 最終更新日: 2024-10-23)

主引用文献

Deng, S.,Xu, Z.,Wang, M.,Hu, J.,Liu, Z.,Zhu, F.,Zheng, P.,Kombe Kombe, A.J.,Zhang, H.,Wu, S.,Jin, T.
Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants.
J.Biol.Chem., 300:107563-107563, 2024

PubMed Abstract: CD8 T cell immunity, mediated by human leukocyte antigen (HLA) and T cell receptor (TCR), plays a critical role in conferring immune memory and protection against viral pathogens. The emergence of SARS-CoV-2 variants poses a serious challenge to the efficacy of current vaccines. Whereas numerous SARS-CoV-2 mutations associated with immune escape from CD8 T cells have been documented, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored. Here, we studied an HLA-A24-restricted NYN epitope (Spike) that elicits broad CD8 T cell responses in COVID-19 patients characterized by a common TCR repertoire. Four natural mutations, N450K, L452Q, L452R, and Y453F, arose within the NYN epitope and have been transmitted in certain viral lineages. Our findings indicate that these mutations have minimal impact on the epitope's presentation by cell surface HLA, yet they diminish the affinities of their respective peptide-HLA complexes (pHLAs) for NYN peptide-specific TCRs, particularly L452R and Y453F. Furthermore, we determined the crystal structure of HLA-A24 loaded with the Y453F peptide (NYNYLFRLF), and subsequently a ternary structure of the public TCR complexed to the original NYN-HLA-A24 (NYNYLYRLF). Our structural analysis unveiled that despite competent presentation by HLA, the mutant Y453F peptide failed to establish a stable TCR-pHLA ternary complex due to reduced peptide: TCR contacts. This study supports the idea that cellular immunity restriction is an important driving force behind viral evolution.

PubMed: 39002680
DOI: 10.1016/j.jbc.2024.107563

実験手法

X-RAY DIFFRACTION (3.2 Å)