Unconventional Sources of Peptides for Antigen Presentation

用于抗原呈递的非常规肽来源

基本信息

批准号：
10224701
负责人：
Scheherazade Sadegh-Nasseri
金额：
$ 54.3万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-17 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10224701
关键词：
Address Adenoviruses Amino Acids Antigen Presentation Autoimmunity B-Lymphocytes Biological Books CD8-Positive T-Lymphocytes Cell surface Cells Cellular Stress Codon Nucleotides Complex Generations Goals HIV Histocompatibility Human Immune response Immunity Immunologic Surveillance Immunologics Initiator Codon Internal Ribosome Entry Site Laboratories Leucine MHC Class I Genes Malignant Neoplasms Mammalian Cell Measures Mediator of activation protein Messenger RNA Methionine Methods Modeling Molecular Mus Normal Cell Open Reading Frames Pathway interactions Peptide Initiation Factors Peptide/MHC Complex Peptides Process Protein Biosynthesis Proteins Reading Frames Reporter Research Ribosomal Interaction Ribosomes Role Sampling Source Stress Surface Testing Text Time Tissue Grafts Tissues Transfer RNA Translating Translations Vaccine Design Viral Virus Work Yeasts antigen processing immunogenicity improved insight leucine-tRNA novel novel strategies pathogen polypeptide ribosome profiling tool tumor

项目摘要

Unconventional sources of peptides for antigen presentation Project Abstract The long term goals of this project are to understand how the antigen processing pathway generates peptide/MHC class I complexes (pMHC I) by cryptic translation. Numerous studies, from different laboratories, have shown that naturally processed pMHC I on the surface of tumors, virally infected cells, transfected or even normal cells arise from regions of mRNAs that were not expected to be translated. The mechanism that allows cells to sample this cryptic source of antigenic precursors versus other conventional sources are poorly understood. Moreover, the conditions that enhance presentation of cryptic peptides in cells are not well defined. Here we will test the hypotheses that (a) cryptic pMHC arise due to translation initiated by a distinct and novel set of tRNAs and ribosomes, (b) expression of cryptic pMHC I is regulated in cells under stress, and (c) the eIF2A translation initiation factor makes a key contribution to the cryptic pMHC I repertoire and immunity. We anticipate that an improved understanding of how cryptic pMHC I are generated will not only provide a means to tap into a novel sources of antigenic peptides and new approaches to vaccine design for intractable viruses and cancer, but will also yield new insights into protein translation and immune surveillance mechanisms.

用于抗原表现的肽的非常规的来源项目摘要该项目的长期目标是了解抗原处理途径如何生成肽/MHC I类配合物（PMHC I）通过隐秘翻译。来自不同的研究实验室已经表明，在肿瘤表面自然处理的PMHC I，病毒感染的细胞，转染甚至正常细胞来自预期不会翻译的mRNA区域。允许细胞采样这种抗原前体的神秘来源的机制与其他机制传统来源对此知之甚少。此外，增强隐秘呈现的条件细胞中的肽的定义不当。在这里，我们将测试（a）由于不同的翻译而产生的（a）神秘PMHC的假设以及新型的TRNA和核糖体集合，（B）在压力下在细胞中调节隐性PMHC I的表达，（c）EIF2A翻译起始因子为密码PMHC i曲目和免疫。我们预计，人们对i的神秘PMHC的产生方式有了改进的了解，不仅会提供一种方法来利用新颖的抗原肽来源和疫苗设计的新方法对于顽固的病毒和癌症，但也将产生对蛋白质翻译和免疫的新见解监视机制。