It is commonly understood that T cells are activated via trans interactions between antigen-specific T-cell receptors (TCRs) and antigenic peptides presented on major histocompatibility complex (MHC) molecules on antigen-presenting cells. By analysing a large number of T cells at the single-cell level on a microwell array, we show that T-cell activation can occur via cis interactions (where TCRs on the T cell interact with the antigenic peptides presented on MHC class-I molecules on the same cell), and that such cis activation can be used to detect antigen-specific T cells and clone their TCR within 4 d. We used the detection-and-cloning system to clone a tumour-antigen-specific TCR from peripheral blood mononuclear cells of healthy donors. TCR cloning by leveraging the cis activation of T cells may facilitate the development of TCR-engineered T cells for cancer therapy.

人们普遍认为，T 细胞是通过抗原特异性 T 细胞受体 (TCR) 和抗原呈递细胞上主要组织相容性复合体 (MHC) 分子上呈递的抗原肽之间的反式相互作用激活的。通过分析微孔阵列上单细胞水平的大量 T 细胞，我们表明 T 细胞激活可以通过顺式相互作用发生（其中 T 细胞上的 TCR 与 MHC I 类分子上呈递的抗原肽相互作用在同一个单元格上），并且这样的独联体激活可用于检测抗原特异性 T 细胞并在 4 天内克隆其 TCR。我们使用检测和克隆系统从健康供体的外周血单核细胞中克隆了肿瘤抗原特异性 TCR。通过利用 T 细胞的顺式激活进行 TCR 克隆可以促进用于癌症治疗的 TCR 工程 T 细胞的开发。