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.
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