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

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Front Immunol. 2019 Nov 6;10:2568. doi: 10.3389/fimmu.2019.02568. eCollection 2019. Gene Expression-Based Identification of Antigen-Responsive CD8⁺ T Cells on a Single-Cell Level.

Fuchs YF¹, Sharma V^1,2, Eugster A¹, Kraus G¹, Morgenstern R¹, Dahl A³, Reinhardt S³, Petzold A³, Lindner A¹, L?bel D¹, Bonifacio E^1,2,4.
Author information

1 Faculty of Medicine, DFG Center for Regenerative Therapies Dresden, Technische Universit?t Dresden, Dresden, Germany. 2 German Center for Diabetes Research (DZD), Paul Langerhans Institute Dresden, Technische Universit?t Dresden, Dresden, Germany. 3 DRESDEN-Concept Genome Center c/o Center for Molecular and Cellular Bioengineering, Technische Universit?t Dresden, Dresden, Germany. 4 Institute of Diabetes and Obesity, Helmholtz Zentrum M?nchen, German Research Center for Environmental Health, Neuherberg, Germany.

Abstract

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.
Copyright ? 2019 Fuchs, Sharma, Eugster, Kraus, Morgenstern, Dahl, Reinhardt, Petzold, Lindner, L?bel and Bonifacio.


KEYWORDS:

CD8+ T cells; CMV pp65; CTL (cytotoxic T lymphocyte); T cell receptor (TCR); antigen-responsive; gene-expression analysis; influenza matrix protein; single-cell

PMID: 31781096 PMCID: PMC6851025 DOI: 10.3389/fimmu.2019.02568
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