ANTIGEN PRESENTATION BY CLASS IB MOLECULES

IB 类分子的抗原呈递

• 批准号: 6235307
• 负责人: IWONA T STROYNOWSKI
• 金额: $ 13.71万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6235307
• 关键词: MHC class I antigen; antigen presentation; cytotoxic T lymphocyte; microorganism antigen; molecular cloning; peptide chemical synthesis; protein biosynthesis; protein sequence; protein structure function; synthetic peptide; tissue /cell culture

Recent advances revealed that classical class I MHC molecules (class Ia), crucial for cell-mediated immunity against pathogens, represent only a small subset of the family of related proteins displaying potential for antigen presentation. The candidate genes for nonclassical class I MHC molecules (class Ib) were identified in all vertebrates including rodents and man. In a few cases class Ib-binding peptides were characterized and their structural features were used to deduce the physiological roles of the presenting molecules. Thanks to this approach, it is now known that murine H-2M3 class Ib molecules participate in the immune response against intracellular pathogen, Listeria monocytogenes. The antigen presentation functions of other class Ib proteins have not been yet defined. We propose to examine the structural properties of self-peptides associated with five different murine class Ib molecules. The specific aims are: 1) to perform a systematic analysis of anchor residues required for binding to Q7 antigen, identify proteins that carry the Q7 binding motif, synthesize the candidate peptide epitopes from known pathogens and test for binding to Q7 2) to overexpress Q6, Q1O, Qa-1 and H-2M3 class Ib complexes in tissue cultured cells and characterize peptides associated with these molecules, using the strategies employed previously by us and our collaborators to define SQ7-bound self-peptides. The results of these studies will provide insights into the biological significance of antigen presentation by class Ib molecules and will generate information relevant to the understand in of their roles in immune response against pathogens and tumors as well as their participation in transplant rejection and in autoimmune reactions.

最近的进展表明，经典的I类MHC分子（Ia类）， 对细胞介导的抗病原体免疫至关重要，仅代表 相关蛋白质家族的一个小子集显示出潜在的 抗原呈递非经典I类MHC的候选基因 在包括啮齿动物在内的所有脊椎动物中鉴定出分子（Ib类 在少数情况下，Ib类结合肽被表征， 它们的结构特征被用来推断生理作用， 呈现分子。由于这种方法，现在已知， 鼠H-2 M3 Ib类分子参与抗 胞内病原体单核细胞增生李斯特菌。抗原呈递 其它Ib类蛋白的功能尚未确定。我们提出 研究与五种蛋白质相关的自身肽的结构特性， 不同的鼠Ib类分子。具体目标是： 1)对所需的锚残基进行系统分析， 与Q7抗原结合，鉴定携带Q7结合基序的蛋白质， 合成来自已知病原体的候选肽表位， 用于结合Q7 2)在组织中过表达Q6、Q1 O、Qa-1和H-2 M3 Ib类复合物 培养细胞并表征与这些分子相关的肽， 使用我们和我们的合作者以前采用的策略， 定义SQ 7结合的自身肽。 这些研究的结果将提供对生物学的见解 Ib类分子抗原提呈意义及意愿 生成与了解其在以下方面的作用相关的信息： 针对病原体和肿瘤的免疫应答及其 参与移植排斥和自身免疫反应。