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