CYTOTOXIC T CELL RESPONSE AGAINST MYCOBACTERIUM AVIUM

鸟分枝杆菌是播散性细菌感染最常见的原因。 艾滋病患者的感染。 M.禽流感病毒主要感染巨噬细胞， 在那里它们被认为以膜结合的方式生存和繁殖 抵抗与溶酶体融合的囊泡。 与大多数细胞内 病原体时，需要细胞介导的免疫来保护免受M. 禽流感 然而，人们对以下方面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。我们有 能够从脾脏培养CD8+细胞毒性T淋巴细胞（CTL） 感染M. avium 这一观察表明， 是分枝杆菌的蛋白抗原， 细胞质按类别在细胞表面进行加工和呈递 I MHC分子。 本提案中概述的实验旨在 为了检验CTL是针对几种 不同M.禽流感病毒蛋白抗原，这些CTL是重要的 抑制M.在后期阶段， 感染我们的方法是生成各种M。鸟类特异性 CTL系，并表征其肽表位特异性， 他们清除M的能力。过继转移至 小鼠 此外，我们将确定是否有要求， 蛋白抗原分泌，以产生M.禽特异性CTL 反应 这些研究将使人们对这两种情况有更深入的了解。 宿主对分枝杆菌感染的反应以及处理和 由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.