CD8+ T CELLS AND MYCOPLASMA TUBERCULOSIS

这份导师科学家奖（KO-8）的申请旨在为M.大卫H. Canadian，医学博士研究培训将由W.医学博士亨利·布姆和克利福德·V·哈丁医学博士博士在凯斯西储大学传染病系和医学系工作。 研究建议将提供重点博士. Canadian的培训概述如下. M.肺结核通过吸入雾化的分枝杆菌在人与人之间传播。 大多数健康的人不会发展为临床结核病。 相反，细胞免疫反应被激活，并能够成功地控制活动性感染。 T细胞在调节细胞免疫应答中起着至关重要的作用。 T细胞亚群（CD 4+、CD 8+、γ δ +）可被分枝杆菌抗原激活，但对不同T细胞亚群在对分枝杆菌的保护性免疫应答中的作用和功能知之甚少。结核虽然CD 4 + T细胞一直是许多研究的焦点，但CD 8 + T细胞是对M的保护性免疫应答中的重要辅助T细胞亚群。结核 最近我们和其他人的研究表明，人CD 8 + T细胞作为M的CTL。结核感染的巨噬细胞产生IFN-γ并被分枝杆菌抗原激活。 目前研究的主要目的是确定刺激人CD 8 + T细胞的分枝杆菌蛋白的库，检查巨噬细胞用于呈递分枝杆菌的抗原加工机制。结核抗原对MHC I类分子的影响，并确定活动性结核病患者中CD 8 + T细胞的功能。 目标是：目标1。目的：研究人α TCR+ CD 8 + T细胞识别分枝杆菌蛋白和多肽的能力。 目标2.确定M.结核感染的巨噬细胞通过MHC I类分子加工和呈递分枝杆菌蛋白。 目标3.目的：研究活动性M患者的功能性CD 8 + T细胞对特异性蛋白和多肽的反应。肺结核感染。

This application for a mentored scientist award (KO-8) seeks 5 years of funding for research training in the cellular immunology and cell biology of M. tuberculosis infection for David H. Canaday, M.D. Research training will be provided by W. Henry Boom, M.D. and Clifford V. Harding, M.D.-Ph.D. in the Division of Infectious Diseases and the Department of Medicine at Case Western Reserve University. The research proposal which will provide the focus for Dr. Canaday's training is outlined below. M. tuberculosis is spread from person to person by inhalation of aerosolized mycobacteria. Most healthy people do not develop clinical tuberculosis. Instead, cellular immune responses become activated and are able to successfully control the active infection. T cells play a crucial role in regulating the cellular immune response. T cell subsets(CD4+, CD8+, gammadelta+), are activated by mycobacterial antigens, yet little is known about the roles and function of the different T cell subsets in the protective immune response to M. tuberculosis. While CD4+ T cells have been the focus of many studies, CD8+ T cells are an important accessory T cell subset in the protective immune response to M. tuberculosis. Recent studies by us and others have demonstrated that human CD8+ T cells serve as CTL for M. tuberculosis infected macrophages, produce IFN-gamma and are activated by mycobacterial antigens. The broad goal of the current studies is to determine the repertoire of mycobacterial proteins which stimulate human CD8+ T cells, to examine the antigen processing mechanism the macrophages use to present M. tuberculosis antigens on MHC class I molecules, and to determine the function of CD8+ T cells in patients with active tuberculosis. The Aims are: Aim 1. To determine the mycobacterial proteins and peptides recognized by human alphabeta TCR+ CD8+ T cells. Aim 2. To determine the mechanism(s) used by M. tuberculosis infected macrophages to process and present mycobacterial proteins by MHC class I molecules. Aim 3. To characterize the functional CD8+ T cell responses to specific proteins and peptides from in patients with active M. tuberculosis infection.