Gene Expression-Based Identification of Antigen-Responsive CD8+ T Cells on a Single-Cell Level

Frontiers in Immunology

Andreas Petzold¹  Andreas Dahl¹  Susanne Reinhardt¹  Anne Eugster²  Yannick F. Fuchs²  Annett Lindner²  Doreen Löbel²  Robert Morgenstern²  Gloria Kraus²  Virag Sharma³  Ezio Bonifacio⁴ 

[1] DRESDEN-Concept Genome Center c/o Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Dresden, Germany;Faculty of Medicine, DFG Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany;German Center for Diabetes Research (DZD), Paul Langerhans Institute Dresden, Technische Universität Dresden, Dresden, Germany;Institute of Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;

关键词: CD8+ T cells;    single-cell;    antigen-responsive;    gene-expression analysis;    CTL (cytotoxic T lymphocyte);    influenza matrix protein;   

DOI  :  10.3389/fimmu.2019.02568

来源: DOAJ

【 摘 要 】

CD8+ T cells are important effectors of adaptive immunity against pathogens, tumors, and self antigens. Here, we asked how human cognate antigen-responsive CD8+ T cells and their receptors could be identified in unselected single-cell gene expression data. Single-cell RNA sequencing and qPCR of dye-labeled antigen-specific cells identified large gene sets that were congruently up- or downregulated in virus-responsive CD8+ T cells under different antigen presentation conditions. Combined expression of TNFRSF9, XCL1, XCL2, and CRTAM was the most distinct marker of virus-responsive cells on a single-cell level. Using transcriptomic data, we developed a machine learning-based classifier that provides sensitive and specific detection of virus-responsive CD8+ T cells from unselected populations. Gene response profiles of CD8+ T cells specific for the autoantigen islet-specific glucose-6-phosphatase catalytic subunit-related protein differed markedly from virus-specific cells. These findings provide single-cell gene expression parameters for comprehensive identification of rare antigen-responsive cells and T cell receptors.

【 授权许可】

Unknown