While CD8+ T-cells are the cornerstone of fighting off infections and tumors, they are also the drivers of multiple autoimmune disorders, such as type-I diabetes. CD8+ T-cells infiltrate the pancreas and destroy the insulin-secreting cells over months to years, leading to insulin-deficiency and hyperglycemia with severe vascular consequences. Despite chronic antigenic exposure, autoimmune CD8+ T-cells appear to remain more functional and cytotoxic than CD8+ T-cells in the context of tumors or chronic infections. One explanation for this divergence could be a differential TCR repertoire comprising different avidities between autoreactive cells and T cells targeting tumor or pathogen related antigens. Using single-cell RNA and TCR-sequencing, we want to sequence the TCR repertoire against the model epitope SIINFEKL, derived from Ovalbumin, in an autoimmune versus an infectious setting. The sequenced TCRs will be re-expressed in reporter cell lines and further characterized for structural and functional avidity. This way we aim to gain more insight in how the autoimmune response is initiated and maintained, paving the way for future therapies to stop the chronicity of the autoimmune destruction.

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