CYTOTOXIC T CELL RESPONSE AGAINST MYCOBACTERIUM AVIUM

禽分枝杆菌是播散性细菌最常见的原因。 艾滋病患者的感染情况。禽类分支杆菌主要感染巨噬细胞， 在那里，它们被认为是在膜结合的环境中生存和繁殖的 拒绝与溶酶体融合的小泡。与大多数细胞内一样 病原体，细胞介导的免疫是针对M。 禽类感染。然而，人们对它的具体作用知之甚少 各种T细胞亚群在清除分枝杆菌感染中的作用。我们有 能够从脾组织中培养CD8+细胞毒性T淋巴细胞(CTL) 感染了鸟型支原体的小鼠。这一观察结果表明， 是可以进入宿主细胞的分枝杆菌蛋白抗原 细胞质，用于按类别在细胞表面加工和呈现 我是MHC分子。这份提案中概述的实验是设计的 测试CTL生成的总体假设 不同的禽类支原体蛋白抗原，这些CTL是重要的 用于抑制禽类支原体在后期的增殖 感染。我们的方法将是生成各种特定于M.avium的 CTL细胞株并鉴定其多肽表位特异性和 它们在领养转移到 老鼠。此外，我们将确定是否需要 分泌蛋白质抗原以产生禽类分枝杆菌特异性CTL 回应。这些研究将导致对两者的更好的理解 宿主对分枝杆菌感染的反应和加工 细胞内病原体产生的蛋白质抗原的呈递。

Mycobacterium avium is the most common cause of disseminated bacterial infection in AIDS patients. M. avium primarily infect macrophages, where they are thought to survive and multiply in membrane-bound vesicles that resist fusion with lysosomes. As with most intracellular pathogens, cell-mediated immunity is required for protection against M. avium infection. However, little is known about the specific roles of the various T cell subsets in clearing mycobacterial infections. We have been able to culture CD8+ cytotoxic T lymphocytes (CTL) from the spleens of mice infected with M. avium. This observation suggests that there are mycobacterial protein antigens that can access the host cell cytoplasm for processing and presentation on the cell surface by class I MHC molecules. The experiments outlined in this proposal are designed to test the overall hypothesis that CTL are generated against several different M. avium protein antigens, and that these CTL are important for inhibiting proliferation of M. avium during the later stages of infection. Our approach will be to generate various M. avium-specific CTL lines and to characterize their peptide epitope specificity and their ability to clear M. avium infections upon adoptive transfer into mice. In addition, we will determine if there is a requirement for protein antigen secretion in order to generate an M. avium-specific CTL response. These studies will lead to a greater understanding of both the host response to mycobacterial infections and the processing and presentation of protein antigens produced by intracellular pathogens.