Chlamydia-induced host protein degradation and its impact on the adaptive immune response.

衣原体诱导的宿主蛋白降解及其对适应性免疫反应的影响。

• 批准号: 9232073
• 负责人: Brian Paul Dolan
• 金额: $ 18.38万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9232073
• 关键词: Adaptive Immune System; Address; Animals; Antibodies; Antigen Presentation; Antigens; Autoantigens; Bacteria; Bacterial Proteins; Binding; CD8-Positive T-Lymphocytes; Cell surface; Cells; Cellular biology; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Cytoplasm; Data; Development; Disease; Ectopic Pregnancy; Environment; Eukaryotic Cell; Family; Future; Generations; Genes; Genital system; Genome; Goals; HLA-A2 Antigen; Histocompatibility Antigens Class I; Human; Immune response; Immune system; Infection; Infertility; Invaded; Lead; Libraries; MHC Class I Genes; Masks; Messenger RNA; Modeling; Mucous Membrane; Mutation; Outcome; Pathology; Pelvic Inflammatory Disease; Peptides; Phenotype; Plasmids; Process; Proteins; Proteome; Reagent; Recombinants; Research Design; Testing; Transcript; Tube; Vaccines; Work; adaptive immune response; combat; design; gain of function; genital infection; major outer membrane protein; mutant; pathogen; prevent; protein degradation; public health relevance; small molecule libraries; tool

 DESCRIPTION (provided by applicant) The obligate intracellular bacteria Chlamydia trachomatis causes serious diseases in both humans and animals. Understanding the mechanisms of its interactions with host cells is essential for controlling infections. C. trachomatis can alter the stability of intracellular host proteins in the cells it infects and the consequences for the host and bacterium are not fully understood. We have determined that infection destabilizes and degrades a model host protein independently of mRNA transcript levels and as a result increases the levels of peptides derived from the host protein. These peptides can bind to MHC class I molecules and be presented to CD8+ T cells at the cell surface. We will determine how C. trachomatis alters the host protein stability by determining which chlamydial genes are responsible for this phenotype. We will also determine if enhancing host peptide presentation decreases the efficiency of the host cell to present peptides derived from chlamydial antigens.

 描述（由申请人提供）专性细胞内细菌沙眼衣原体在人类和动物中引起严重疾病。了解其与宿主细胞相互作用的机制对于控制感染至关重要。C.沙眼衣原体可改变其感染的细胞中的细胞内宿主蛋白的稳定性，并且对宿主和细菌的后果尚未完全了解。我们已经确定，感染不依赖于mRNA转录水平而使模型宿主蛋白不稳定并降解，结果增加了源自宿主蛋白的肽的水平。这些肽可以与MHC I类分子结合，并在细胞表面呈递给CD8+ T细胞。我们将确定C。沙眼衣原体通过确定哪些衣原体基因负责这种表型来改变宿主蛋白质的稳定性。我们还将确定增强宿主肽呈递是否降低宿主细胞呈递衣原体抗原衍生肽的效率。