Analysis of TCR (T cells receptor) repertoire is an essential element in our understanding of the immune response. The main body of knowledge of T cell biology has been created by studying T cell clones, cultures and accessory molecules facilitating TCR/peptide/MHC interaction. The T cell repertoires of naïve, activated and memory T-cells are intensively investigated in human and experimental animals. It has been shown that after thymic selection, T-cells fill up the pool of naïve cells. Only T cells, expressing TCR optimal for peptide/MHC interaction, undergo Ag-specific activation, functional maturation and apoptosis. Despite our knowledge of molecules mediating T-cell interaction with APC or target cells, there are several intriguing and unresolved issues. The mechanisms that define how cells are recruited for Ag elimination and how T cell memory compartment is created and maintained are the subjects of our research. We study the CD8 T cell recall response to influenza A and EBV viral peptides presented in the context of HLA-A2.1. In-depth analysis of the epitope specific immune responses allowed us to conclude that the repertoire of responding CD8 T cell clones has a more complex structure than has been previously thought. We showed that not only the amino acid sequence in the CDR3 region, but CDR3 length, V- and J-region sequence usage and T cell precursor frequency are selection factors for optimal anti-viral immune response. Polyclonality of the T cells, specific to the influenza viral peptide, can be described as a fractal system indicating a very complex structure of the responding naïve and memory cells. We proposed and are currently exploring a model that avoidance of a finely focused TCR repertoire removes the possibility of pathogen evasion.
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Email: joan.veinot@umassmed.edu
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Analysis of TCR (T cells receptor) repertoire is an essential element in our understanding of the immune response. The main body of knowledge of T cell biology has been created by studying T cell clones, cultures and accessory molecules facilitating TCR/peptide/MHC interaction. The T cell repertoires of naïve, activated and memory T-cells are intensively investigated in human and experimental animals. It has been shown that after thymic selection, T-cells fill up the pool of naïve cells. Only T cells, expressing TCR optimal for peptide/MHC interaction, undergo Ag-specific activation, functional maturation and apoptosis. Despite our knowledge of molecules mediating T-cell interaction with APC or target cells, there are several intriguing and unresolved issues. The mechanisms that define how cells are recruited for Ag elimination and how T cell memory compartment is created and maintained are the subjects of our research. We study the CD8 T cell recall response to influenza A and EBV viral peptides presented in the context of HLA-A2.1. In-depth analysis of the epitope specific immune responses allowed us to conclude that the repertoire of responding CD8 T cell clones has a more complex structure than has been previously thought. We showed that not only the amino acid sequence in the CDR3 region, but CDR3 length, V- and J-region sequence usage and T cell precursor frequency are selection factors for optimal anti-viral immune response. Polyclonality of the T cells, specific to the influenza viral peptide, can be described as a fractal system indicating a very complex structure of the responding naïve and memory cells. We proposed and are currently exploring a model that avoidance of a finely focused TCR repertoire removes the possibility of pathogen evasion.
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