Portrayal T-cell Memory: Robustness and Complexity

关于对特定流感肽的回忆（记忆）细胞毒性T细胞应答的研究已经表明，应答T细胞库可以是复杂的。TCR库的复杂性可与对病原体的稳健免疫应答相关，这对于疫苗接种策略设计是重要的。TCR库的复杂性，其可以随着时间的推移而改变，相对于抗原再攻击，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剧目的复杂性在个人和群体水平。为了测试这些描述在不同实验场景中的适用性，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，从个体和群体水平上表征基因组库的复杂性，并确定影响基因组库动态变化的因素。根据密尔沃基公共卫生部门提供的已识别流感病例，将动态库变化与供体的抗流感滴度水平以及病原体再暴露的季节性概率相关联，可估计近期流感暴露对个体和人群水平TCR库复杂性的影响。库建模将得到其他中心组件获得的实验数据的支持。统一而专门的剧目分析的结果将为所有三个提供反馈 集中组件并统一它们以实现中心的目标。

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.