000K  utf8
1100  $c2025
1500  eng
2050  urn:nbn:de:gbv:8:3-2025-00013-7
3000  Efstratiou, Artemis
4000  Dynamics of the T cell receptor repertoire of a small vertebrate in response to infection$hChristian-Albrechts-Universität zu Kiel  [Efstratiou, Artemis]
4030  Kiel$nChristian-Albrechts-Universität zu Kiel
4209  The adaptive immune system of vertebrates is central to defense against pathogens. It relies on T cells, which respond to pathogenic exposure via T cell receptors (TCRs) recognizing antigens presented by Major Histocompatibility Complex (MHC) molecules. MHC variability and TCR repertoire diversity are crucial for the initiation and efficacy of the adaptive immune response, respectively. Building upon recent advancements in TCR repertoire analysis using Next Generation Sequencing (NGS), this thesis explores the TCR repertoire dynamics during infection in the three-spined stickleback, an experimental model species encompassing natural genetic variation. Chapter 1 focuses on developing a reproducible NGS-based protocol for reliable MHC genotyping, and highlights the importance of pipeline optimization for accurate allele expression analysis via use of DNA and RNA data. Chapter 2 investigates the TCR repertoire in response to controlled helminth infection, and demonstrates significant non-MHC genetic effects on its diversity. Hints of parasite-induced suppression of TCR compartments are discussed in an eco-evolutionary context. Public, MHC-unrestricted TCRs provide indirect evidence for previously uncharacterized non-conventional T cells. Lastly, Chapter 3 examines the TCR repertoire in a semi-natural setting, following stickleback exposure to its natal environment. Findings include robust TCR activation coinciding with multiple infections, and notable sex-based differences in repertoire diversity. Age-related changes in repertoire composition align with known mammalian aging patterns. Overall, this thesis advances our understanding of TCR repertoire infection dynamics, emphasizing strong genetic and environmental factors shaping its diversity. This work also offers insights into a mode of TCR repertoire organization conserved throughout vertebrate evolution, based on innate-like T cells, the functional importance of which is yet to be fully elucidated.
4950  https://nbn-resolving.org/urn:nbn:de:gbv:8:3-2025-00013-7$xR$3Volltext$534
4961  https://macau.uni-kiel.de/receive/macau_mods_00005533
5051  570
5550  Adaptive immune receptor repertoire
5550  Evolution
5550  Immune system
5550  Infectious disease
5550  Major Histocompatibility Complex
5550  Next Generation Sequencing
5550  T cell receptor