人类TLR9的合作PS-oligo激活的特征
Adam J Pollak1, Luyi Zhao1, Stanley T Crooke1
1Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA.
Molecular therapy. Nucleic acids
|September 7, 2023
概括
单链基酸寡核酸 (PS-oligos) 协同激活托尔类受体9 (TLR9),即使没有CpG动机. 这种合作结合增强了先天的免疫反应,揭示了对TLR9激活机制的新见解.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 奥利冈核酸治疗药物 治疗药物
背景情况:
- 众所周知,单链基酸寡核酸 (PS-oligos) 能够激活托尔类受体9 (TLR9),从而启动先天性免疫反应.
- 激活可以通过PS-oligos中的正规非甲基化CpG基因或非CpG基因进行调解.
- 结构数据表明TLR9具有两个不同的结合点,暗示了潜在的合作激活机制.
研究的目的:
- 通过人类细胞系中的PS-oligos对来证明和描述TLR9的合作激活.
- 引入和评估新的PS-oligo对,包括CpG和非CpG组合,用于合作TLR9激活.
- 研究PS-oligos对TLR9.9的结合部位和激活原始化效应.
主要方法:
- 利用人类细胞系研究PS-oligo与TLR9.9的相互作用.
- 设计并测试了各种PS-oligo对 (CpG和非CpG) 来评估合作激活.
- 分析了单个PS-oligos对随后的TLR9激活的原始效应.
主要成果:
- 通过特定的PS-oligo对证明了合作性TLR9激活,这表明它在不同的TLR9位点结合.
- 确定了新的CPG和非CPGPS-oligo对,表现出合作激活.
- 观察到一些PS-oligos可以启动TLR9以加强其他PS-oligos的激活.
- 发现现有的TLR9激活模型无法完全解释人类TLR9和PS-oligo系统的数据.
结论:
- PS-oligos与TLR9的合作结合增强了免疫激活,提供了新的治疗策略.
- PS-oligos可以与TLR9的不同部位结合,从而导致协同激活.
- TLR9激活是复杂的,可以通过原始化效应来调节,需要更新的机械模型.
- 需要进一步的研究,以精确地绘制人类TLR9.9上的PS-oligo结合位点.
相关概念视频
Formation of Lipopolysaccharides
40
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
40
T Cell Activation and Clonal Selection
801
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
801
Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K
T Cell Types and Functions
1.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.1K
B Cell Activation and Differentiation
1.8K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.8K
Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K


