ANTIGEN PROCESSING IN LOWER EUKARYOTIC CELLS

低等真核细胞中的抗原加工

• 批准号: 5200577
• 负责人: J W YEWDELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200577
• 关键词: Culicidae; MHC class I antigen; antigen presentation; cytotoxic T lymphocyte; endoplasmic reticulum; intracellular transport; protein transport; tissue /cell culture

CD8+ T cells recognize class I molecules of the major histocompatibility complex (MHC) bearing peptides of 8 to 10 residues derived from cytosolic proteins. These cells are a bulwark of host defenses to infectious agents and tumors, and if we are to improve existing vaccines and develop new vaccines and treatments for infectious and neoplastic diseases, it is critical to understand antigen processing, the mechanism by which antigenic peptides are generated by cells and delivered to class I molecules. Although there has been great progress in understanding antigen processing in the past 5 years, there remains much to be learned. The strategy of this project is to delineate what we do not know. We are expressing the known constituents of the antigen processing machinery in mosquito cells and determining whether this is sufficient to reconstitute antigen processing to a level seen in mammalian cells. Insects do not have a MHC and do not, therefore, have any of the specialized machinery associated with antigen processing. If these cells can process antigens under these conditions, this would indicate that we have identified the major components of antigen processing; if they cannot, it would mean that further discoveries are required. In the past year, we have found that class I molecules expressed in cells derived from an invertebrate fail to properly assemble with peptides delivered to the ER, suggesting the existence of accessory molecules in higher eukaryotic cells that load peptides onto class I molecules.

CD8+ T 细胞识别主要组织相容性的 I 类分子 含有源自胞质的 8 至 10 个残基的肽的复合物 (MHC) 蛋白质。 这些细胞是宿主防御感染的堡垒 病原体和肿瘤，如果我们要改进现有疫苗并开发 针对传染病和肿瘤疾病的新疫苗和治疗方法 对于了解抗原加工至关重要，其机制 抗原肽由细胞产生并传递至 I 类 分子。 虽然理解上有了很大的进步 过去5年的抗原加工研究，还有很多值得学习的地方。 这个项目的策略是描绘我们不知道的东西。 我们是 表达抗原加工机器的已知成分 蚊子细胞并确定这是否足以重建 抗原加工达到哺乳动物细胞中可见的水平。 昆虫没有 有 MHC，因此没有任何专门的机制 与抗原加工有关。 如果这些细胞可以处理抗原 在这些条件下，这表明我们已经确定 抗原加工的主要组成部分；如果他们不能，那就意味着 需要进一步的发现。 在过去的一年里，我们发现 在源自无脊椎动物的细胞中表达的 I 类分子 未能与递送至 ER 的肽正确组装，表明 高等真核细胞中存在辅助分子 将肽附着到 I 类分子上。