T LYMPHOCYTE RESPONSE TO VIRAL ANTIGENS

这项建议旨在调查加工后的 在感染细胞中产生的流感病毒抗原性部分 由人的CD4T淋巴细胞识别，并表征 病毒蛋白被加工和呈递的细胞内途径 对人类T淋巴细胞的影响。建议的研究是我们 正在进行的关于人类T淋巴细胞反应的特征的工作 病毒多肽。我们的实验方法是首先描述 天然加工的流感血凝素和核衣壳多肽 通过层析和质谱学手段与人类白细胞抗原DRV11结合。在……里面 相关研究，病毒感染对自身谱系的影响 将评估感染细胞中与MHC II类分子结合的多肽 以及病毒抗原形式的影响，例如分离的病毒 多肽或从头表达的病毒蛋白，在结构上 在抗原提呈细胞中产生的自然处理的多肽。 将努力开发能够追踪细菌形成的试剂。 多肽MHC复合体在感染细胞中的表达及评价其作用 病毒加工过程中抗原表位外的氨基酸 多肽和抗原肽的形成。在相关的 研究中，我们将研究病毒糖蛋白靶向于 溶酶体抗原处理室及其作用机制 胞质病毒蛋白被处理并呈现为与 人类MHC II类分子。这项提案中概述的实验 将提供关于自然加工的 病毒抗原性部分识别人T淋巴细胞及其机制 通过它们在感染病毒的细胞中产生。这样的信息 将在病毒疫苗设计中具有立竿见影的重要性和长期意义 了解感染过程中免疫功能的意义。

This proposal is designed to investigate the structure of the processed influenza viral antigenic moieties generated in infected cells which are recognized by human CD4+ T lymphocytes and to characterize the intracellular pathways by which viral proteins are processed and presented to human T lymphocytes. The proposed studies are an extension of our ongoing work on the characterization of the human T lymphocyte response to viral polypeptides. Our experimental approach is to first characterize the naturally processed influenza hemagglutinin and nucleocapsid peptides bound to HLA DRwll by chromatographic and mass spectroscopic means. In related studies, the impact of virus infection on the spectrum of self peptide bound to MHC class II molecules in infected cells will be assessed as well as the effect of viral antigen form, e.g. isolated viral polypeptides or de novo expressed viral protein, on the structure of the naturally processed peptides generated in antigen presenting cells. Efforts will be made to generate reagents which can tract the formation of peptide MHC complexes in the infected cell and to evaluate the effect of aminoacids outside of an antigenic epitope on the processing of the viral polypeptides and the formation of the antigenic peptide. In related studies, we will examine the pathways of viral glycoprotein targeting to the lysosomal antigen processing compartment and the mechanism by which cytosolic viral proteins are processed and presented in association with human MHC class II molecule. The experiments outlined in this proposal will provide new information on the structure of the naturally processed viral antigenic moieties recognized human T lymphocytes, and the mechanism by which they are generated in virus infected cells. Such information will be of immediate importance in viral vaccine design and of long-term significance in understanding immune function during infection.