ANTIGEN PROCESSING IN LOWER EUKARYOTIC CELLS

CD8T细胞识别主要组织相容性的I类分子 含8-10个残基的胞浆多肽的复合体(MHC) 蛋白质。这些细胞是宿主防御传染病的堡垒。 制剂和肿瘤，如果我们要改进现有的疫苗和开发 传染病和肿瘤疾病的新疫苗和治疗方法，它 是理解抗原处理的关键，抗原处理的机制 抗原肽由细胞产生并递送到I类 分子。尽管在理解上有了很大的进步 抗原处理在过去的5年里，还有很多需要学习的地方。 这个项目的策略是勾勒出我们不知道的东西。我们是 表达抗原处理机制的已知成分 蚊子细胞和确定这是否足以重建 抗原处理达到在哺乳动物细胞中看到的水平。昆虫不会 有MHC，因此没有任何专门的机械 与抗原处理有关。如果这些细胞能够处理抗原 在这种情况下，这将表明我们已经确定了 抗原处理的主要组成部分；如果它们不能，这将意味着 还需要进一步的发现。在过去的一年里，我们发现 在来自无脊椎动物的细胞中表达的I类分子 未能与交付给急诊室的多肽正确组装，表明 高等真核细胞中辅助分子的存在 多肽结合到I类分子上。

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.