Portrayal T-cell Memory: Robustness and Complexity

对特定流感多肽的回忆(记忆)细胞毒性T细胞反应的研究表明，反应的T细胞谱系可能是复杂的。TCR谱系的复杂性可能与对病原体的强大免疫反应有关，这对于疫苗策略设计是重要的。TCR谱系的复杂性，可以随着时间的推移而随着抗原的重新挑战而变化，必须适当地表征。这需要对复杂的人类免疫系统进行全面的正式描述。在这个项目中，我们将开发一个通用的方法来表征个人和群体水平上的曲目复杂性。为了测试这些描述对不同实验场景的适用性，我们将生成剧目开发和维护的数学模型。使用建模，我们将进一步澄清我们的工作定义，检查所提出的方法的有效性 在不同的模拟条件下，在个体和群体水平上表征曲目的复杂性，并确定影响曲目动态变化的因素。根据密尔沃基公共卫生部门提供的已确定的流感病例，将库的动态变化与捐赠者的抗流感滴度水平与病原体再次暴露的季节性概率相关联，将有助于在个人和人群层面上估计最近的流感暴露对TCR库复杂性的影响。曲目建模将得到在其他中心组件中获得的实验数据的支持。统一但专门的曲目分析的结果将向所有三个人提供反馈 使各组成部分居中并统一起来，以实现中心的目标。

Studies on the recall (memory) cytotoxic T cell response to a specific influenza peptide have shown that the responding T cell repertoire can be complex. Complexity of TCR repertoires can be associated with robust immune responses to pathogens, which are important for vaccination strategy design. Complexity of TCR repertoires, which can change over time with respect to an antigen re-challenge, have to be properly characterized. This requires a comprehensive formal description of complex human immune repertoires. In this project, we will develop a generalized approach for characterization of repertoire complexity on individual and population levels. To test applicability of such descriptions for different experimental scenarios, we will generate mathematical models of repertoires development and maintenance. Using modeling we will further clarify our working definitions, examine validity of the proposed approach for characterization of repertoire complexity on individual and population levels under various simulate conditions, and determine factors influencing dynamic repertoire changes. Correlating dynamic repertoire changes with the level of anti-influenza titers of the donors, with the seasonal probability of pathogen re-exposure based on identified influenza cases provided by the Milwaukee Public Health Department will allow estimation of the impact of recent influenza exposure on TCR repertoire complexity at both individual and population levels. The repertoire modeling will be supported by experimental data obtained in other Center components. The results of uniform, yet specialized repertoire analysis will provide a feedback to all three Center components and unify them in achieving the Center's goals.