Cellular Immune Surveillance of Intracellular bacteria

描述（由申请人提供）：我们研究的长期目标是了解1)免疫系统识别哪些细菌抗原以及哪些因素影响细菌中的抗原靶标库，2)哪些免疫机制具有保护性以及宿主免疫效应物如何抵消特定毒力因子从而产生保护性免疫，以及3)细菌逃避免疫监视的可能性和机制。在本应用中，我们将以单核增生李斯特菌（Listeria monocytogenes， LM）为模型：

DESCRIPTION (provided by applicant): The long-term objectives of our study are to understand 1) what bacterial antigens are recognized by the immune system and what factors influence the repertoire of antigenic targets in bacteria, 2) what immune mechanisms are protective and how host immune effectors counteract specific virulence factors to bring about protective immunity, and 3) how likely and by what mechanisms bacteria may escape immune surveillance. In this application, we will use Listeria monocytogenes (LM) as a model to: 1. Examine how regulation of gene expression affects the ability of a bacterial protein to induce immune responses and to serve as a protective target. The results of this study will help us define the complexity of the antigenic repertoire of bacteria and develop general guidelines for the selection of antigenic targets for vaccination. 2. Test a model that protective immunity against LM is determined by a race between CTL-mediated cytolysis and bacterial spread into neighboring cells. This model is suggested by our finding that CTL cytolysis functions to counteract LM's virulence strategy of direct cell-cell spread. We will test several predictions of this model and in doing so we hope to identify mechanisms of immune protection that correlate with bacterial virulence strategies. 3. Investigate the possibility that antagonist peptides may play a role in shaping the repertoire of T cell targets and in allowing bacterial escape of CTL surveillance. Our preliminary results have demonstrated the in vivo effect of TCR antagonism on T cell responses and protective immunity. We will study several aspects of agonist/antagonist interactions in vivo during infection. The results of these studies will help in our understanding of the complex interactions between bacteria and their hosts that determine the outcome of infection, and will have important implications for the design of effective vaccines and the selection of protective vaccine antigens.