Unconventional Sources of Peptides for Antigen Presentation

用于抗原呈递的非常规肽来源

• 批准号: 9978688
• 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
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-17 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978688
• 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

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.

抗原呈递的非常规多肽来源