Unconventional Sources of Peptides for Antigen Presentation

用于抗原呈递的肽的非常规来源 项目摘要 该项目的长期目标是了解抗原加工途径如何产生 肽/MHC I类复合物（pMHC I）。许多研究，从不同的 实验室，已经表明，在肿瘤，病毒感染的细胞， 转染的或甚至正常的细胞产生于预期不被翻译的mRNA区域。 允许细胞对这种抗原前体的神秘来源进行采样的机制， 对传统来源了解甚少。此外，增强隐藏的呈现的条件 细胞中的肽没有很好地定义。 在这里，我们将测试的假设，（a）神秘的pMHC产生由于翻译启动的一个独特的 和新的一组tRNA和核糖体，（B）在应激下细胞中隐蔽pMHC I的表达受到调节， 和（c）eIF 2A翻译起始因子对隐蔽性pMHC I库做出关键贡献， 免疫力 我们预计，对pMHC I如何产生的更好理解不仅会 提供了一种方法，以挖掘抗原肽的新来源和疫苗设计的新方法 对于顽固的病毒和癌症，但也将产生新的见解蛋白质翻译和免疫 监督机制。

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.