The T Cell Repertoire–Diversifying Enzyme TSSP Contributes to Thymic Selection of Diabetogenic CD4 T Cell Specificities Reactive to ChgA and IAPP Autoantigens

摘要: Multiple studies highlighted the overtly self-reactive T cell repertoire in diabetes-prone NOD mouse. This autoreactivity has primarily been linked to defects apoptosis induction during central tolerance. Previous suggested that thymus-specific serine protease (TSSP), a putative expressed by cortical thymic epithelial cells and dendritic cells, may edit of self-peptides presented MHC class II molecules shapes CD4 repertoire. To gain further insight into role TSSP selection endogenous self-Ags, we examined development thymocytes expressing distinct diabetogenic TCRs sharing common specificity environment lacking TSSP. Using mixed bone marrow chimeras, evaluated effect deficiency confined different stromal on differentiation chromogranin A–reactive BDC-2.5 BDC-10.1 or islet amyloid polypeptide–reactive TCR BDC-6.9 BDC-5.2.9. We found resulted deficient positive induced deletion TCRs, but it did not affect BDC-5.2.9 TCRs. Hence, subtle generation self-peptide ligands directing development. These results provide additional evidence for activity as novel mechanism promoting autoreactive development/accumulation