Bacterial and Liposomal Antigen Processing

描述（由申请人提供）：I类MHC Ag交叉处理允许外源性或液泡Ag处理并提呈CD8+ T细胞。交叉加工是淋巴结中树突状细胞（dc）启动CD8+幼稚T细胞所必需的。交叉加工的一个鲜为人知但潜在的关键作用是允许被空泡病原体（如结核分枝杆菌（MTB））感染的非淋巴器官中的细胞向CD8+效应T细胞呈递病原体来源的抗原，以引发细胞因子产生或细胞溶解功能。dc和巨噬细胞都可能携带MTB，并可能向CD8+效应T细胞呈递MTB Ags，从而使CD8+ T细胞有助于抑制MTB感染。研究方向：研究细菌银加工的基本机制，主要关注mhc - 1交叉加工。选择结核分枝杆菌作为一种模式生物，除了其作为人类病原体的意义之外，它还代表了处理孔内病原体的良好模式。有待解决的问题：不知道哪些mtb感染的装甲运兵车具有交叉处理功能；这对产生免疫反应和免疫逃避具有重要意义。我们不了解空泡病原体（如MTB）交叉加工的机制，也没有研究生理上重要的肺apc的交叉加工功能。假设：空泡生物（如结核分枝杆菌）的交叉加工允许CD8+ T细胞识别受感染的细胞，有助于宿主防御。dc和巨噬细胞都可以交叉递呈Ags到效应T细胞，尽管它们可能使用不同的交叉加工机制，接受不同的病原体调控，在免疫应答中发挥不同的作用。目的1探讨结核分枝杆菌交叉处理的基本机制。目的2探讨肺APCs的交叉加工功能。目的3研究toll样受体、干扰素和结核分枝杆菌的交叉加工调控。外行意义：这些研究将发现CD8+ T细胞对结核病病原体的免疫识别机制，这有助于对抗结核病感染。这将增加我们对结核病发病机制的了解，并有助于制定针对结核病和其他疾病的增强疫苗设计或免疫治疗策略。

DESCRIPTION (provided by applicant): Class I MHC Ag cross processing allows exogenous or vacuolar Ags to be processed for presentation to CD8+ T cells. Cross processing is essential for priming of CD8+ naive T cells by dendritic cells (DCs) in lymph nodes. A less recognized but potentially critical role of cross processing is to allow cells in non-lymphoid organs that are infected with vacuolar pathogens, e.g. Mycobacterium tuberculosis (MTB), to present pathogen-derived antigens to CD8+ effector T cells to elicit cytokine production or cytolytic function. DCs and macrophages may both harbor MTB and may hypothetically present MTB Ags to CD8+ effector T cells, allowing CD8+ T cells to contribute to containment of MTB infection. Research direction: This grant is to study basic mechanisms of bacterial Ag processing with a primary focus on MHC-I cross processing. MTB is selected as a model organism that represents an excellent model for processing of intravacuolar pathogens in addition to its significance as a human pathogen. Questions to be solved: We do not know which MTB-infected APCs have cross processing function; this has important implications for generation of immune responses vs. immune evasion. We do not understand mechanisms for cross processing of vacuolar pathogens, e.g. MTB, and cross processing functions of physiologically important lung APCs have not been investigated. Hypothesis: Cross processing of vacuolar organisms (e.g. MTB) allows recognition of infected cells by CD8+ T cells, contributing to host defense. DCs and macrophages may both cross present Ags to effector T cells, although they may use different cross processing mechanisms, undergo different regulation by pathogens, and play different roles in immune responses. Aim 1 addresses basic mechanisms of cross processing of MTB. Aim 2 investigates the cross processing functions of lung APCs. Aim 3 addresses regulation of cross processing by Toll-like receptors, interferons and MTB. Significance in lay terms: These studies will discover mechanisms that allow immune recognition of the causative agent of tuberculosis by CD8+ T cells, which help fight tuberculosis infection. This will increase our understanding of tuberculosis pathogenesis and aid development of strategies for enhanced vaccine design or immunotherapy for tuberculosis and other diseases.