Portrayal T-cell Memory: Robustness and Complexity

对回忆（记忆）细胞毒性T细胞对特定流感肽反应的研究表明，反应的T细胞库可能是复杂的。TCR库的复杂性可能与对病原体的强大免疫反应有关，这对疫苗接种策略设计很重要。TCR谱的复杂性可以随着时间的推移而随着抗原的再攻击而改变，必须适当地表征。这需要对复杂的人体免疫功能进行全面的正式描述。在这个项目中，我们将开发一种在个体和群体水平上表征曲目复杂性的通用方法。为了测试这些描述对不同实验场景的适用性，我们将生成库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

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.