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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 subsets. We find small but significant differences in the TCR repertoire parameters between the maturation stages, which recapitulate known differentiation pathways leading to the CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    subtypes. These differences can be simulated by simple models of selection acting linearly on the sequence features. We find no evidence of specific sequences or sequence motifs or features that are suppressed by negative selection. These results favour a collective or statistical model for T-cell self non-self discrimination, where negative selection biases the repertoire away from self recognition, rather than ensuring lack of self-reactivity at the single-cell level.\n                  <\/jats:p>","DOI":"10.7554\/elife.81622","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T06:00:17Z","timestamp":1674194417000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.81622","source":"Crossref","is-referenced-by-count":34,"title":["Quantifying changes in the T cell receptor repertoire during thymic development"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-2631","authenticated-orcid":true,"given":"Francesco","family":"Camaglia","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02feahw73","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de physique de l\u2019\u00c9cole normale sup\u00e9rieure, CNRS, PSL University, Sorbonne Universit\u00e9, and Universit\u00e9 de Paris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"Ryvkin","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-8469","authenticated-orcid":true,"given":"Erez","family":"Greenstein","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomit","family":"Reich-Zeliger","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-3970","authenticated-orcid":true,"given":"Benny","family":"Chain","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02jx3x895","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infection and Immunity, University College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5456-9361","authenticated-orcid":true,"given":"Thierry","family":"Mora","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02feahw73","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de physique de l\u2019\u00c9cole normale sup\u00e9rieure, CNRS, PSL University, Sorbonne Universit\u00e9, and Universit\u00e9 de Paris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2686-5702","authenticated-orcid":true,"given":"Aleksandra M","family":"Walczak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02feahw73","id-type":"ROR","asserted-by":"publisher"}],"name":"Laboratoire de physique de l\u2019\u00c9cole normale sup\u00e9rieure, CNRS, PSL University, Sorbonne Universit\u00e9, and Universit\u00e9 de Paris","place":["Paris, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nir","family":"Friedman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunology, Weizmann Institute of Science","place":["Rehovot, Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"bib1","article-title":"Bayesian Entropy Estimation for Countable Discrete Distributions","volume-title":"arXiv","author":"Archer","year":"2014","unstructured":"Archer E, Park IM, Pillow J. 2014. 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