Unconventional Sources of Peptides for Antigen Presentation

用于抗原呈递的非常规多肽来源 项目摘要 这个项目的长期目标是了解抗原处理途径是如何产生的。 多肽/MHC I类复合体(PMHC I)通过隐蔽翻译。无数的研究，来自不同的 实验室已经证明，在肿瘤表面，病毒感染的细胞， 转基因甚至是正常的细胞都来自不被翻译的mRNAs区域。 允许细胞对这种神秘的抗原前体来源进行采样的机制 人们对传统来源知之甚少。此外，增强隐语呈现的条件 细胞中的多肽没有被很好地定义。 在这里，我们将测试假设：(A)神秘的pMHC是由于由不同的 和一组新的tRNAs和核糖体，(B)隐藏的pMHC I在应激条件下在细胞中的表达受到调控， 以及(C)eIF2A翻译起始因子对神秘的pMHC I谱系起到关键作用，并且 豁免权。 我们预计，对神秘的pMHC I是如何生成的更好的理解不仅将 提供了一种利用抗原肽的新来源和疫苗设计的新方法的手段 治疗难治的病毒和癌症，但也将对蛋白质翻译和免疫产生新的见解 监视机制。

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.