BIOSYNTHESIS OF NOVEL CLASS IB MOLECULES

新型 IB 类分子的生物合成

• 批准号: 6198839
• 负责人: TED Howard HANSEN
• 金额: $ 30.88万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6198839
• 关键词: MHC class I antigen; antibody; antigenic peptide transporter; calnexin; calreticulin; endoplasmic reticulum; intermolecular interaction; laboratory mouse; laboratory rabbit; molecular chaperones; protein biosynthesis; serology /serodiagnosis

DESCRIPTION (Adapted from the Investigator's abstract): Classical class I MHC molecules (class Ia) are expressed on all nucleated cells and their roles in antigen presentation to CD8+ T-cells during infection or malignancy are well documented. By contrast, there are a large number of non-classical (class Ib) molecules that typically have a restricted tissue distribution and undefined functions. However, recent studies have implicated certain class Ib molecules in such specialized and diverse functions as resistance to bacterial infection (mouse M3), immune recognition by NK cells (mouse Qa-1 and human HLA-E), embryo implantation (mouse Qa-2 and human HLA-G), gut immunity (mouse TL) and iron homeostasis (mouse and human HFE). Interestingly, certain of these functions involve peptide presentation by class Ib molecules (e.g. M3/formylated peptides and Qa-1/signal peptides) whereas other class Ib molecules (e.g. HFE) appear not to bind peptides. In addition, for many class Ib molecules (e.g. the newly discovered MR1) the peptide binding status is unknown, although their implied structures suggests that they could bind peptides. In spite of the very interesting and diverse biology of the class Ib family, little is known of their biosynthesis due to lack of good reagents. In this application the investigator proposes to introduce a serological epitope into six different class Ib molecules that will specifically identify their respective pre-assembled forms. Using this technique he will have the opportunity to study the interactions of class Ib molecules with their respective assembly partners as well as members of the ER peptide loading complex (tapasin, TAP, calreticulin and Erp57). These studies will determine how disparate chaperone interactions contribute to the unique assembly and tissue expressions displayed by functionally diverse class Ib molecules.

描述(改编自《调查者摘要》)：经典I类MHC 分子(Ia类)在所有有核细胞上都有表达，它们在 感染或恶性肿瘤时CD8+T细胞的抗原提呈良好 有记录在案。相比之下，有大量的非古典(Ib类) 通常具有受限的组织分布和未定义的分子 功能。然而，最近的研究表明，某些Ib类分子 在抵抗细菌感染等特殊而多样的功能中 (小鼠M3)，NK细胞的免疫识别(小鼠Qa-1和人HLA-E)，胚胎 植入(小鼠Qa-2和人HLA-G)、肠道免疫(小鼠TL)和铁 动态平衡(小鼠和人的HFE)。有趣的是，其中某些函数 涉及Ib类分子的肽递呈(例如M3/甲酰化肽 和Qa-1/信号肽)，而其他Ib类分子(例如HFe)出现 不是用来结合多肽的。此外，对于许多Ib类分子(例如，新的 已发现的MR1)肽结合状态未知，尽管它们暗示 结构表明它们可以结合多肽。尽管有非常多 类Ib的有趣而多样的生物学，鲜为人知 由于缺乏良好的试剂，它们的生物合成。在此应用程序中， 研究人员建议将一个血清学表位引入六个不同的 Ib类分子将专门识别它们各自的 预装好的模板。使用这项技术，他将有机会学习 Ib类分子与其各自组装伙伴的相互作用 以及ER多肽负载复合体的成员(Tapasin，TAP， 钙网蛋白和Erp57)。这些研究将确定不同的伴侣如何 相互作用有助于显示独特的组装和组织表达 通过功能不同的Ib类分子。