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Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire

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Abstract

The lifespan of T cells is determined by continuous interactions of their T cell receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by different subsets of antigen-presenting cells (APC). In the thymus, developing thymocytes are positively selected through recognition of self-pMHC presented by cortical thymic epithelial cells (cTEC). They are subsequently negatively selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature T cells is likewise controlled by the interaction of their TCR with self-pMHC complexes presented by lymph node stromal cells while they may be tolerized by DC presenting tissue-derived self-antigens. To perform these tasks, the different subsets of APC are equipped with distinct combination of antigen processing enzymes and consequently present specific repertoire of self-peptides. Here, we discuss one such antigen processing enzyme, the thymus-specific serine protease (TSSP), which is predominantly expressed by thymic stromal cells. In thymic DC and TEC, TSSP edits the repertoire of peptide presented by class II molecules and thus shapes the CD4 T cell repertoire.

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Funding

This work was supported in part by the “Institut National de la Santé et de la Recherche Médicale” and the “Centre National de la Recherche Scientifique” and by grants from The Agence Nationale de la Recherche (ANR-10-BLAN-1332, ANR-13-BSV1–0017), the French MS society (ARSEP), the Medical Research Foundation (FRM), The European Foundation for the Study of Diabetes/Sanofi, The European Foundation for the Study of Diabetes/Lilly, The Juvenile Diabetes Research Foundation International, and the IdEx Toulouse University and the Midi-Pyrénées Région to SG.

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  1. INSERM, U1043, 31300, Toulouse, France

    Sylvie Guerder & Chervin Hassel

  2. CNRS, UMR5282, 31300, Toulouse, France

    Sylvie Guerder & Chervin Hassel

  3. Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, 31300, Toulouse, France

    Sylvie Guerder & Chervin Hassel

  4. INSERM UMR1043, Centre de Physiopathologie de Toulouse Purpan, CHU Purpan, BP 3028, 31024, Toulouse CEDEX 3, France

    Sylvie Guerder

  5. Aix-Marseille University, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France

    Alice Carrier

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Correspondence to Sylvie Guerder.

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This article is part of the Topical Collection on Biology and Evolution of Antigen Presentation

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Guerder, S., Hassel, C. & Carrier, A. Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire. Immunogenetics 71, 223–232 (2019). https://doi.org/10.1007/s00251-018-1078-y

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