Proteolytic Generation Of Antigenic Peptides

抗原肽的蛋白水解生成

• 批准号: 8555798
• 负责人: JACK R BENNINK
• 金额: $ 61.38万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8555798
• 关键词: Antigen Presentation; Antigens; CD8B1 gene; Cell Nucleus; Complex; Cytosol; Event; Generations; Goals; Histocompatibility Antigens Class I; Lead; Life Cycle Stages; Molecular Structure; Parasites; Peptide Hydrolases; Peptides; Play; Production; Proteins; Proteolysis; Role; T-Lymphocyte; Ubiquitin; Viral; Viral Proteins; Virus; antigen processing; base; immunogenicity; interest; multicatalytic endopeptidase complex; protein folding; response

CD8 expressing T cells play a critical role in eradicating intracellular parasites such as viruses. CD8 positive T cells recognize MHC class I molecules in a complex with peptides of 8 to 10 residues derived from viral proteins located in the cytosol. There is tremendous interest in the mechanism by which peptides are generated. Indirect evidence implicates proteasomes in the generation of antigenic peptides. Proteasomes are abundant macromolecular structures present in the cytosol and nucleus, and have multiple protease activities. They are thought to be responsible for energy dependent proteolysis in which ubiquitin plays a prominent role in targeting proteins for destruction. In this project we examine the contribution of proteasomes to the production of antigenic peptides as well as their importance to viral life cycles. Another goal is to identify sequences that enhance the immunogenicity of proteins by increasing their capacity to generate antigenic peptides. This year we have found that the efficiency of antigen presentation varies dependent on whether the antigen derives from cellular or virus encoded proteins. The results suggest that the class I antigen-processing machinery can distinguish folded proteins based on the precise details of their synthesis to modulate antigen presentation efficiency.

表达T细胞的CD8在根除细胞内寄生虫（例如病毒）中起着关键作用。 CD8阳性T细胞识别MHC I类分子中的MHC I类分子，其肽的肽为8至10个残基，这些残基来自位于胞质溶胶中的病毒蛋白。对产生肽的机制具有极大的兴趣。间接证据暗示蛋白酶体在抗原肽的产生中。蛋白酶体是细胞质和核中存在的丰富的大分子结构，并且具有多种蛋白酶活性。人们认为它们是依赖能量的蛋白水解的原因，其中泛素在靶向蛋白质的破坏中起着重要作用。在这个项目中，我们研究了蛋白酶体对抗原肽生产的贡献，以及它们对病毒生命周期的重要性。另一个目标是通过增加产生抗原肽的能力来识别蛋白质的免疫原性的序列。今年，我们发现抗原呈递的效率取决于抗原是源自细胞还是病毒编码蛋白的效率。 结果表明，I类抗原处理机械可以根据其合成的精确细节来区分折叠蛋白，以调节抗原表现效率。