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.