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Previous studies suggested that thymus-specific serine protease (TSSP), a putative serine protease expressed by cortical thymic epithelial cells and thymic dendritic cells, may edit the repertoire of self-peptides presented by MHC class II molecules and shapes the self-reactive CD4 T cell repertoire. To gain further insight into the role of TSSP in the selection of self-reactive CD4 T cells by endogenous self-Ags, we examined the development of thymocytes expressing distinct diabetogenic TCRs sharing common specificity in a thymic environment lacking TSSP. Using mixed bone marrow chimeras, we evaluated the effect of TSSP deficiency confined to different thymic stromal cells on the differentiation of thymocytes expressing the chromogranin A\u2013reactive BDC-2.5 and BDC-10.1 TCRs or the islet amyloid polypeptide\u2013reactive TCR BDC-6.9 and BDC-5.2.9. We found that TSSP deficiency resulted in deficient positive selection and induced deletion of the BDC-6.9 and BDC-10.1 TCRs, but it did not affect the differentiation of the BDC-2.5 and BDC-5.2.9 TCRs. Hence, TSSP has a subtle role in the generation of self-peptide ligands directing diabetogenic CD4 T cell development. These results provide additional evidence for TSSP activity as a novel mechanism promoting autoreactive CD4 T cell development\/accumulation in the NOD mouse.<\/jats:p>","DOI":"10.4049\/jimmunol.1401683","type":"journal-article","created":{"date-parts":[[2015,7,25]],"date-time":"2015-07-25T03:05:08Z","timestamp":1437793508000},"page":"1964-1973","source":"Crossref","is-referenced-by-count":16,"title":["The T Cell Repertoire\u2013Diversifying Enzyme TSSP Contributes to Thymic Selection of Diabetogenic CD4 T Cell Specificities Reactive to ChgA and IAPP Autoantigens"],"prefix":"10.1093","volume":"195","author":[{"given":"Christophe","family":"Viret","sequence":"first","affiliation":[{"name":"Centre de Physiopathologie de Toulouse Purpan , Toulouse F-31300 ,","place":["France"]},{"name":"INSERM , U1043, Toulouse F-31300 ,","place":["France"]},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte Recherche 5282 , Toulouse F-31300 ,","place":["France"]},{"name":"Universit\u00e9 Toulouse III Paul-Sabatier , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim","family":"Mahiddine","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie de Toulouse Purpan , Toulouse F-31300 ,","place":["France"]},{"name":"INSERM , U1043, Toulouse F-31300 ,","place":["France"]},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte Recherche 5282 , Toulouse F-31300 ,","place":["France"]},{"name":"Universit\u00e9 Toulouse III Paul-Sabatier , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocky Lee","family":"Baker","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Haskins","sequence":"additional","affiliation":[{"name":"Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health , Denver, CO 80206"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Guerder","sequence":"additional","affiliation":[{"name":"Centre de Physiopathologie de Toulouse Purpan , Toulouse F-31300 ,","place":["France"]},{"name":"INSERM , U1043, Toulouse F-31300 ,","place":["France"]},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte Recherche 5282 , Toulouse F-31300 ,","place":["France"]},{"name":"Universit\u00e9 Toulouse III Paul-Sabatier , Toulouse F-31300 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,1]]},"reference":[{"key":"2025030704080581900_r1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0092-8674(00)81106-X","article-title":"Insulin-dependent diabetes mellitus","volume":"85","author":"Tisch","year":"1996","journal-title":"Cell"},{"key":"2025030704080581900_r2","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1146\/annurev.iy.13.040195.001143","article-title":"Genetic control of autoimmune diabetes in the NOD mouse","volume":"13","author":"Wicker","year":"1995","journal-title":"Annu. 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