High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8 + T cells
High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8 + T cells
Abstract Although critical to T cell function, antigen specificity is often omitted in high-throughput multi-omics based T cell profiling due to technical challenges. We describe a high-dimensional, tetramer-associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene-expression, and surface-protein expression from tens of thousands of single cells. Using polyclonal CD8+ T cells with known antigen specificity and TCR sequences, we demonstrated over 98% precision for detecting the correct antigen specificity. We also evaluated gene-expression and phenotypic differences among antigen-specific CD8+ T cells and characterized phenotype signatures of influenza- and EBV-specific CD8+ T cells that are unique to their pathogen targets. Moreover, with the high-throughput capacity of profiling hundreds of antigens simultaneously, we applied TetTCR-SeqHD to identify antigens that preferentially enrich cognate CD8+ T cells in type 1 diabetes patients compared to healthy controls, and discovered a TCR that cross reacts between diabetic and microbiome antigens. TetTCR-SeqHD is a powerful approach for profiling T cell responses.
He Chenfeng、Chen Eunise、Kulkarni-Date Mrinalini、Jiang Ning、Xia Amanda Y.、Ma Ke-Yue、Schonnesen Alexandra A.、Sun Eric、Sebastian Katherine R、Balderas Robert
Department of Biomedical Engineering, the University of Texas at AustinDepartment of Nutritional Sciences, the University of Texas at Austin. AustinDepartment of Internal Medicine, Dell Medical School, the University of Texas at AustinInterdisciplinary Life Sciences Graduate Programs, the University of Texas at Austin||Department of Biomedical Engineering, the University of Texas at Austin||Department of Oncology, Dell Medical School, the University of Texas at AustinDepartment of Molecular Biosciences, the University of Texas at AustinInterdisciplinary Life Sciences Graduate Programs, the University of Texas at Austin||Beijing Advanced Innovation Center for Biomedical EngineeringDepartment of Biomedical Engineering, the University of Texas at AustinDepartment of Biomedical Engineering, the University of Texas at AustinDepartment of Internal Medicine, Dell Medical School, the University of Texas at AustinBecton Dickinson
基础医学生物科学研究方法、生物科学研究技术
He Chenfeng,Chen Eunise,Kulkarni-Date Mrinalini,Jiang Ning,Xia Amanda Y.,Ma Ke-Yue,Schonnesen Alexandra A.,Sun Eric,Sebastian Katherine R,Balderas Robert.High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8 + T cells[EB/OL].(2025-03-28)[2025-05-04].https://www.biorxiv.org/content/10.1101/2021.03.04.433914.点此复制
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