美国德克萨斯大学奥斯汀分校Ning Jiang小组实现抗原特异性CD8⁺ T细胞的高通量和高维度单细胞分析。这一研究成果于2021年11月22日在线发表在国际学术期刊《自然—免疫学》上。

Title: High-throughput and high-dimensional single-cell analysis of antigen-specific CD8+ T cells

Author: Ma, Ke-Yue, Schonnesen, Alexandra A., He, Chenfeng, Xia, Amanda Y., Sun, Eric, Chen, Eunise, Sebastian, Katherine R., Guo, Yu-Wan, Balderas, Robert, Kulkarni-Date, Mrinalini, Jiang, Ning

Issue&Volume: 2021-11-22

Abstract: Although critical to T cell function, antigen specificity is often omitted in high-throughput multiomics-based T cell profiling due to technical challenges. We describe a high-dimensional, tetramer-associated T cell antigen receptor (TCR) sequencing (TetTCR-SeqHD) method to simultaneously profile cognate antigen specificities, TCR sequences, targeted gene expression and surface-protein expression from tens of thousands of single cells. Using human polyclonal CD8+ T cells with known antigen specificity and TCR sequences, we demonstrate over 98% precision for detecting the correct antigen specificity. We also evaluate gene expression and phenotypic differences among antigen-specific CD8+ T cells and characterize phenotype signatures of influenza- and Epstein–Barr virus-specific CD8+ T cells that are unique to their pathogen targets. Moreover, with the high-throughput capacity of profiling hundreds of antigens simultaneously, we apply TetTCR-SeqHD to identify antigens that preferentially enrich cognate CD8+ T cells in patients with type 1 diabetes compared to healthy controls and discover a TCR that cross-reacts with diabetes-related and microbiome antigens. TetTCR-SeqHD is a powerful approach for profiling T cell responses in humans and mice.

DOI: 10.1038/s41590-021-01073-2

Source: https://www.nature.com/articles/s41590-021-01073-2