Tconv and Treg gene expression and repertoire analysis of ZAC mice

Autoimmune diseases, such as rheumatoid arthritis (RA), are believed to be caused, in part, by a defect in the selection of T cells. Developing T cells undergo a process known as “negative selection” where self-derived proteins are presented to the cells; those that react to the self-peptides are either eliminated, or develop into regulatory T cells (Tregs), which suppress immune responses by conventional T cells (Tconvs). In order to study self-reactive T cell receptors (TCRs), and their likely target antigens, we performed single cell repertoire analysis in ZAC mice with impaired TCR signaling. We sequenced TCR and transcriptomes of Treg and Tconv single cells from arthritic ZAC mice spleen (n=2). We discovered a cluster of pro-inflammatory Th17 Tconv cells in ZAC spleens that was absent in WT mice. ZAC Th17 TCRs showed clonal expansion. Different mice had different TCR sequences, which is expected. Overall design: Single cell gene expresion and repertoire data from splenic Tconvs from two arthritic ZAC mice. These mice are also Foxp3 GFP reporter