Antigen-specific CD4+ T cell responses to influenza

描述(由申请人提供)：这项建议的总体目标是更好地了解在流感小鼠模型中抗原特异性CD4+T细胞反应的功能相关性和发展。增强和操纵CD4+T细胞反应的能力对传染病、癌症和艾滋病的免疫治疗具有重要意义。在这项研究中，包含在血凝素或神经氨酸酶中插入的1-Ab背景上定义的CD4+表位的流感病毒将使用反向遗传学产生。然后，这些病毒将被用来通过四聚体染色、细胞内细胞因子染色和ELISPOT分析来表征抗原特异性CD4T细胞在C57BL/6流感感染模型的初级、次级和记忆阶段的发育、动力学、表型和效应功能。这些数据将被用来确定流感模型中抗原特异性CD4+T细胞的效应机制。利用转基因T细胞受体小鼠，也将确定CD4+T细胞反应的数量和质量对流感初次和二次感染的影响。最后，我们将研究在不同遗传背景下，流感抗原特异性与非相关抗原启动对过敏反应的影响。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to better understand the functional relevance and development of antigen-specific CD4+ T cell responses in the mouse model of influenza. The ability to potentiate and manipulate CD4+ T cell responses has important implications for immune therapy in infectious diseases, cancer and AIDS. In this study, influenza viruses containing defined CD4+ epitopes on the 1-Ab background inserted in either the hemagglutinin or neuraminadase will be generated using reverse genetics. These viruses will then be used to characterize the development, kinetics, phenotype and effector function of antigen-specific CD4 T cells in primary, secondary and memory phases of the C57BL/6 model of influenza infection using tetramer staining, intracellular cytokine staining and ELISPOT analyses. These data will be used to determine the effector mechanisms of antigen-specific CD4+ T cells in the influenza model. Using a transgenic T cell receptor mouse, the effect of the quantity and quality of CD4+ T cell responses on influenza primary and secondary infection will also be determined. Finally, the effects of antigen-specific vs. unrelated antigen priming by influenza on allergic responses on different genetic backgrounds will be examined.