Tssp-deficient mice, a model to identify new essential diabetogenic antigens

TSSP is a novel protease suspected to edit the peptide repertoire presented by MHC class II molecules in the thymus. Prss16, the gene coding for TSSP is linked to a diabetes susceptibility locus in Human.We found that TSSP-deficient NOD mice are fully protected from spontaneous diabetes and severe insulitis. Disease resistance is due to the intra-thymic deletion of some, yet to characterize, diabetogenic CD4 T cells. Collectively our results show that in the thymus, TSSP prevents the presentation of some self-antigens and consequently impairs central tolerance induction to some self antigens.

Interest / Relevance: This model should permit the identification of new islet antigens that are essential in the development of spontaneous diabetes.Design novel immunotherapy
Keywords: autoimmunity , type 1 diabetes , tolerance , immunotherapy , mouse model
Viret C. Lamare C. Guiraud M. Fazilleau N. Bour A. Malissen B. Carrier A. and Guerder S. (2011). Thymus-specific serine protease contributes to the diversification of the functional endogenous CD4 T cell receptor repertoire. The Journal of experimental medicine 208 3-11.Viret C. Leung-Theung-Long S. Serre L. Lamare C. Vignali D.A. Malissen B. Carrier A. and Guerder S. (2011). Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice. The Journal of clinical investigation 121 1810-1821.



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Inserm Transfert
Research Tools
Species: Mice
Genotype: Prss16tm1Mal/Prss16tm1Mal
Strain: TSSP° NOD mice
Genetic Background: NOD N20
Applications: Autoimmune diabetes
Rare disease: No
Last update: 08/07/2024

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