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. Single cell gene expresion and repertoire data from splenic Tconvs from two arthritic ZAC mice. These mice are also Foxp3 GFP reporter

自身免疫性疾病（Autoimmune diseases）如类风湿关节炎（rheumatoid arthritis, RA），被认为部分由T细胞（T cells）选择缺陷引发。发育中的T细胞会经历名为“阴性选择”的过程：自身源性蛋白被呈递给这些细胞，识别自身肽的T细胞要么被清除，要么分化为调节性T细胞（regulatory T cells, Tregs）——这类细胞可抑制常规T细胞（conventional T cells, Tconvs）介导的免疫应答。为探究自身反应性T细胞受体（T cell receptors, TCRs）及其潜在靶抗原，我们对TCR信号受损的ZAC小鼠开展了单细胞TCR谱系分析。我们对患有关节炎的ZAC小鼠脾脏内调节性T细胞与常规T细胞的TCR及转录组进行了测序（n=2）。研究发现，ZAC小鼠脾脏中存在一簇促炎性Th17常规T细胞，该细胞群在野生型（Wild Type, WT）小鼠中并未出现。ZAC小鼠的Th17型TCRs呈现克隆扩增特征，且不同小鼠的TCR序列存在差异，这与预期相符。本数据集包含两只患有关节炎的ZAC小鼠脾脏常规T细胞的单细胞基因表达数据与TCR谱系数据，该类小鼠同时为Foxp3 GFP报告小鼠。