IMMUNE RESPONSE TO HIV-1 ENCODED ANTIGENS IN MICE

这项建议的目的是研究： 1.CD-4内化与CD-4的关系 对HIV-1感染的敏感性。我们将人CD-4细胞 基因导入小鼠T细胞杂交瘤，其中一个杂交瘤可以 感染了HIV-1病毒。CD-4分子的细胞生物学将是 重点研究了CD-4的作用机制 内部化。T的容量与T的关系 内化CD-4分子的细胞杂交瘤及其敏感性 将对HIV-1感染进行调查。我们将调查 HIV-1感染对CD-4载体T细胞活化的影响 杂交瘤。 2.HIV-1基因表达对机体生理的影响 淋巴细胞和单核细胞。我们将HIV的TATIII基因-- L转化为小鼠B细胞淋巴瘤(A20)，为小鼠特异性抗原 T细胞杂交瘤(7E2)和小鼠单核细胞瘤(P388D1)。 之所以选择这些细胞系，是因为它们的表面抗原， 抗原的特异性，抗体和淋巴因子的产生 被很好地刻画出来了。此外，这些细胞类型是相似的 对已知感染艾滋病毒的细胞类型--L、T细胞、单核细胞 和一些B细胞。我们会继续研究这些措施的影响。 TATIII基因对细胞表面抗原表达的影响 这些转基因细胞系的生理学。 3.L编码抗原在小鼠体内的免疫应答。 我们用talIII转基因细胞株免疫正常小鼠。 并产生抗原特异性CTL和多克隆特异性抗血清 转TATIII基因的细胞系。至关重要的表位 对于CTL的诱导，将被鉴定。我们计划 鉴定由talIII基因诱导的新蛋白质。这个 这些实验的结果应该为以下方面提供有用的见解 Ta III基因的作用方式与免疫应答 反对TATIII基因产物。我们计划用HIV免疫小鼠-- L感染小鼠细胞株及T细胞介导的体液免疫研究 体内对HIV-L感染细胞的免疫应答。 这些研究利用了体内和体外的艾滋病毒-L模型 小鼠体内的感染。这些模型系统是专门设计的 为便于发现艾滋病毒-L进入宿主的机制 细胞及HIV-L基因表达对细胞生理的影响 和功能。通过研究对小鼠细胞系的免疫反应 要么是单独基因转基因，要么是艾滋病毒感染--L， 我们将研究单个病毒基因的作用模式 以及宿主对艾滋病病毒的免疫反应-L。这些实验 将为了解艾滋病毒的发病机制提供基本见解--L 感染。

The objectives of this proposal are to study: 1. The relationship between CD-4 Internalization and susceptibility to HIV-1 Infection. We transfected the human CD-4 gene into murine T cell hybridomas, one of these hybridomas can be infected by HIV-1. The cell biology of the CD-4 molecules will be studied with particular emphasis on the mechanism of CD-4 internalization. The relationship between the capacity of the T cell hybridomas to internalize CD-4 molecules and their sensitivity to HIV-1 infection will be investigated. We will investigate the effects of HIV-1 infection on the activation of CD-4 bearing T cell hybridomas. 2. Effects of HIV-1 gene expression on the physiology of lymphocytes and monocytes. We transfected the tatIII gene of HIV- l into a murine B cell lymphoma (A20), a murine antigen specific T cell hybridoma (7E2) and a murine monocyte tumor line (P388D1). These cell lines were chosen because their surface antigens, antigen specificities, and antibody and lymphokine production have been well characterized. In addition, these cell types are similar to the cell types known to be infected by HIV-l, T cells, monocytes and some B cells. We will continue to study the effects of the tatIII gene on the expression of surface antigens and the physiology of these transfected cell lines. 3. Immune responses against HIV-l encoded antigens in mice. We have immunized normal mice with tatIII transfected cell lines and generated antigen specific CTL and polyclonal antisera specific for tatIII transfected cell lines. The epitopes that are essential for the elicitation of CTL will be identified. We plan to characterize the new proteins induced by the tatIII gene. The results from these experiments should provide useful insights into the mode of action of the tatIII gene and the immune responses against tatIII gene products. We plan to immunize mice with HIV- l infected murine cell lines and study T cell mediated and humoral immune responses to HIV-l infected cells in vivo. These investigations utilize in vivo and in vitro models of HIV-l infection in the murine system. These model systems are designed to facilitate discovery of the mechanisms of HIV-l entry into host cells and the effects of HIV-l gene expression on cell physiology and function. By studying the immune response to murine cell lines either transfected with individual genes or infected with HIV-l, we will be studying the mode of action of individual viral genes and the host immune responses against HIV-l. These experiments will provide fundamental insights into the pathogenesis of HIV-l infection.