ANTIGEN PROCESSING IN LOWER EUKARYOTIC CELLS

CD 8 + T细胞识别主要组织相容性I类分子 具有来自细胞溶质的8至10个残基的肽的MHC复合物（MHC） proteins. 这些细胞是宿主防御传染性疾病的堡垒。 如果我们要改进现有的疫苗， 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，抗原加工的机制是 抗原肽由细胞产生并递送至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，还有很多东西需要学习。 这个项目的策略是描述我们不知道的东西。 我们 表达抗原加工机制的已知成分， 蚊子细胞，并确定这是否足以重建 抗原加工到哺乳动物细胞中可见的水平。 昆虫不 有一个主要组织相容性复合体，因此，没有任何专门的机制， 与抗原加工有关。 如果这些细胞能处理抗原 在这种情况下，这将表明我们已经确定， 抗原处理的主要组成部分;如果它们不能， 需要进一步的发现。 在过去的一年里，我们发现 I类分子在无脊椎动物的细胞中表达 不能与递送到ER的肽正确组装，这表明 在高等真核细胞中存在辅助分子， 肽到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.