相关实验视频
Updated: Jun 21, 2025
13:00
Engineering Antiviral Agents via Surface Plasmon Resonance
Published on: June 14, 2022
2.3K
对SARS-CoV-2 Spike Y453F变异的杀手T细胞表位中的免疫逃逸的结构性见解
Shasha Deng1, Zhihao Xu2, Meihua Wang2
1Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Hefei, Anhui, P.R. China.
The Journal of biological chemistry
|July 13, 2024
概括
在NYN表位内SARS-CoV-2突变极小地影响HLA呈现,但降低T细胞受体结合亲和力. 结构分析显示TCR-pHLA复合体形成受损,突出显示细胞免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 由人类白细胞抗原 (HLA) 和T细胞受体 (TCR) 介导的CD8+T细胞免疫对于病毒保护至关重要.
- 新出现的SARS-CoV-2变种由于免疫逃生突变,挑战了疫苗的有效性.
- 突变对表位特异性TCR识别的分子影响在很大程度上是未知的.
研究的目的:
- 研究HLA-A24受限制的NYN表位体内自然突变对TCR识别的分子效应.
- 确定这些突变如何影响-HLA (pHLA) 复合物的稳定性和TCR结合亲和力.
- 阐明改变TCR-pHLA相互作用的结构基础.
主要方法:
- 研究了一种受HLA-A24限制的NYN表位 (Spike448-456) 和其自然变体 (N450K,L452Q,L452R,Y453F).
- 通过HLA和pHLA-TCR结合亲缘关系评估突变对表位表现的影响.
- 确定了HLA-A24与Y453F的结晶结构和TCRNYN-I与NYN-HLA-A24的三元复合体.
主要成果:
- 在NYN表位内发生的四种自然突变对HLA呈现的影响很小.
- 突变,特别是L452R和Y453F,显著降低了pHLA与NYN特定TCR的结合亲和力.
- 结构分析显示,由于减少了:TCR接触,Y453F突变未能形成稳定的TCR-pHLA三元复合体.
结论:
- SARS-CoV-2 突变可以通过减少 TCR 识别亲和力来逃避 CD8+ T 细胞免疫力,而不仅仅是 HLA 呈现.
- 结构洞察力揭示了T细胞识别受损的机制.
- 细胞免疫限制是病毒进化的重要驱动因素.
相关概念视频
01:29Immune Response Against Viral Pathogens
770
The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
770
02:50Conjugated Proteins
18.3K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.3K