biostudies-literatureCamaglia FCNRS-WeizmannAgence Nationale de la RechercheEuropean Research Councile81622https://www.ebi.ac.uk/biostudies/studies/S-EPMC9934861biostudies-literatureUnknown12One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. However, the impact of thymic selection on the TCR repertoire is poorly understood. Here, we use transgenic Nur77-mice expressing a T-cell activation reporter to study the repertoires of thymic T cells at various stages of their development, including cells that do not pass selection. We combine high-throughput repertoire sequencing with statistical inference techniques to characterize the selection of the TCR in these distinct subsetseLifeQuantifying changes in the T cell receptor repertoire during thymic development.PMC993486180 primeCOG 724208ANR-19-CE45-0018Ryvkin AChain BMora TReich-Zeliger SWalczak AMCamaglia FGreenstein EFriedman NfalseQuantifying changes in the T cell receptor repertoire during thymic development.One of the feats of adaptive immunity is its ability to recognize foreign pathogens while sparing the self. During maturation in the thymus, T cells are selected through the binding properties of their antigen-specific T-cell receptor (TCR), through the elimination of both weakly (positive selection) and strongly (negative selection) self-reactive receptors. However, the impact of thymic selection on the TCR repertoire is poorly understood. Here, we use transgenic Nur77-mice expressing a T-cell activation reporter to study the repertoires of thymic T cells at various stages of their development, including cells that do not pass selection. We combine high-throughput repertoire sequencing with statistical inference techniques to characterize the selection of the TCR in these distinct subsets2023-01-01T00:00:00Z2023 Jan2025-04-20T03:03:39.529Z2025-04-20T03:03:39.529ZS-EPMC99348613666122010.7554/eLife.81622