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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI062627-01
Application #
6847304
Study Section
Special Emphasis Panel (ZAI1-PA-I (S1))
Project Start
2004-09-30
Project End
2009-08-31
Budget Start
2004-09-15
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$338,150
Indirect Cost
Name
Bloodcenter of Wisconsin, Inc.
Department
Type
DUNS #
057163172
City
Milwaukee
State
WI
Country
United States
Zip Code
53233
Alarcon Falconi, T M; Cruz, M S; Naumova, E N (2018) The shift in seasonality of legionellosis in the USA. Epidemiol Infect 146:1824-1833
Yassai, Maryam B; Demos, Wendy; Gorski, Jack (2017) Structural and Mechanistic Implications of Rearrangement Frequencies within Human TCRBV Genes. J Immunol 199:1142-1152
Gil, Anna; Yassai, Maryam B; Naumov, Yuri N et al. (2015) Narrowing of human influenza A virus-specific T cell receptor ? and ? repertoires with increasing age. J Virol 89:4102-16
Zhou, Vivian; Yassai, Maryam B; Regunathan, Jeyarani et al. (2013) The functional CD8 T cell memory recall repertoire responding to the influenza A M1(58-66) epitope is polyclonal and shows a complex clonotype distribution. Hum Immunol 74:809-17
Bonacci, Benedetta; Edwards, Brandon; Jia, Shuang et al. (2012) Requirements for growth and IL-10 expression of highly purified human T regulatory cells. J Clin Immunol 32:1118-28
Kumar, Pawan; Bartoszek, Allison E; Moran, Thomas M et al. (2012) High-throughput detection method for influenza virus. J Vis Exp :
Levy, H; Wang, X; Kaldunski, M et al. (2012) Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun 13:593-604
Petrova, Galina; Ferrante, Andrea; Gorski, Jack (2012) Cross-reactivity of T cells and its role in the immune system. Crit Rev Immunol 32:349-72
Petrova, Galina V; Gorski, Jack (2012) Cross-reactive responses to modified M1??-?? peptides by CD8? T cells that use noncanonical BV genes can describe unknown repertoires. Eur J Immunol 42:3001-8
Baumgartner, Christina K; Yagita, Hideo; Malherbe, Laurent P (2012) A TCR affinity threshold regulates memory CD4 T cell differentiation following vaccination. J Immunol 189:2309-17

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