Antigen-specific Tregs are potent and specific suppressors of pathogenic autoreactivity. A/Prof. Ooi has developed a unique platform that combines the use of peptide binding assays, high-throughput single cell TCR sequencing and lentiviral Treg transduction to enable the generation of therapeutic antigen-specific TCR-Tregs. In this talk, they applied this platform to developing a treatment for SLE. In SLE, autoreactivity to the Smith (Sm) antigen leads to more severe disease manifestations including the development of lupus nephritis. Using the TCR-Treg platform, A/Prof. Ooi's team identified the precise Sm-derived autoepitope driving disease and generated Sm-specific TCR-Tregs (Sm-Tregs). They showed that these Sm-Tregs could suppress patient derived autoimmunity in in vitro assays and could treat disease in a novel humanised mouse model of lupus nephritis.