Defining the Protective CD4+ T cell Responses to Salmonella typhimurium

对粘膜病原体的适应性免疫反应仍然知之甚少，这限制了针对重要人类病原体（如B类生物恐怖制剂沙门氏菌）的新疫苗的开发。我建议使用新开发的试剂来检测沙门氏菌特异性CD4 T细胞在肠粘膜和全身组织中的激活和记忆。本建议的具体目标是：目标1。确定沙门氏菌蛋白在不同位置的差异表达是否允许启动位点特异性CD4 T细胞。目标2。检查沙门氏菌特异性记忆CD4 T细胞发育是否在快速清除有毒细菌后受损。我的初步数据表明，我可以开发新的MHC ii类四聚体试剂来跟踪粘膜和全身沙门氏菌特异性T细胞在体内的反应。我的两个具体目标将使用尖端技术，第一次检查内源性沙门氏菌特异性T细胞的启动和记忆发展。

The adaptive immune response to mucosal pathogens is still poorly understood, limiting the development of new vaccines for important human pathogens such as the category B bioterrorism agent Salmonella. I propose to use newly developed reagents to examine the Salmonella-specific CD4 T cells activation and memory in the intestinal mucosa and systemic tissues. The specific aims of this proposal are: Aim 1. Determine whether differential expression of Salmonella proteins in different locations allows priming of site-specific CD4 T cells. Aim 2. Examine whether Salmonella-specific memory CD4 T cell development is impaired after rapid clearance of virulent bacteria. My preliminary data demonstrate that I can develop novel MHC class-II tetramer reagents to track the mucosal and systemic Salmonella-specific T cell response in vivo. My two specific aims will use cutting-edge technology, to examine the priming, and memory development of endogenous Salmonella- specific T cells for the first time.