T LYMPHOCYTE RESPONSE TO VIRAL ANTIGENS

该建议旨在研究处理的结构 在感染细胞中产生的流感病毒抗原部分， 识别的人CD4+ T淋巴细胞，并表征 病毒蛋白加工和呈递的细胞内途径 to human人T淋巴细胞. 拟议的研究是我们的一个扩展， 正在进行的关于人T淋巴细胞对 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肽 通过色谱和质谱手段结合到HLADRwII。 在 相关研究表明，病毒感染对自身谱系的影响 将评估与感染细胞中MHCII类分子结合的肽 以及病毒抗原形式，例如分离的病毒 多肽或从头表达的病毒蛋白质，在结构上， 在抗原呈递细胞中产生的天然加工肽。 将努力产生可以追踪以下物质的形成的试剂： 肽MHC复合物在感染的细胞，并评估的影响， 抗原表位外的氨基酸对病毒加工的影响 多肽和抗原肽的形成。 在相关 研究，我们将研究病毒糖蛋白靶向的途径， 溶酶体抗原处理区室和机制， 细胞溶质病毒蛋白被加工并与 人MHC II类分子。 本提案中概述的实验 将提供新的信息的结构， 病毒抗原部分识别人T淋巴细胞， 通过该方法它们在病毒感染的细胞中产生。 此类信息 将在病毒疫苗设计中具有直接重要性， 对了解感染过程中的免疫功能具有重要意义。

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.