BIOSYNTHESIS OF NOVEL CLASS IB MOLECULES

描述（改编自研究者摘要）：经典I类MHC 分子（Ia类）在所有有核细胞上表达， 在感染或恶性肿瘤期间，抗原呈递给CD 8 + T细胞是良好的。 记录在案。相比之下，有大量的非经典（Ib类） 分子通常具有有限的组织分布和不确定的 功能协调发展的然而，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 稳态（小鼠和人HFE）。有趣的是，这些功能 涉及Ib类分子的肽呈递（例如M3/甲酰化肽 和Qa-1/信号肽），而其它Ib类分子（例如HFE）出现 而不是结合肽。此外，对于许多Ib类分子（例如，新的 发现MR 1）肽结合状态是未知的，虽然他们暗示 结构表明它们可以结合肽。尽管非常 有趣的和多样的生物学类Ib家庭，鲜为人知的是， 它们的生物合成由于缺乏良好的试剂。在本申请中， 研究者建议将血清学表位引入六种不同的 Ib类分子将特异性地识别它们各自的 预组装的形式。使用这种技术，他将有机会学习 Ib类分子与它们各自的组装伙伴的相互作用 以及ER肽装载复合物（tapasin，TAP， 钙网蛋白和Erp 57）。这些研究将确定不同的伴侣 相互作用有助于显示独特的组装和组织表达 功能多样的Ib类分子。

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.