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

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-la...

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Bibliographic Details
Published in:	Frontiers in immunology Vol. 10; p. 2568
Main Authors:	Fuchs, Yannick F, Sharma, Virag, Eugster, Anne, Kraus, Gloria, Morgenstern, Robert, Dahl, Andreas, Reinhardt, Susanne, Petzold, Andreas, Lindner, Annett, Löbel, Doreen, Bonifacio, Ezio
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 06-11-2019
Subjects:	antigen-responsive CD8+ T cells CTL (cytotoxic T lymphocyte) gene-expression analysis Immunology influenza matrix protein single-cell CD8+ T cells CMV pp65 antigen-responsive single-cell gene-expression analysis influenza matrix protein CTL (cytotoxic T lymphocyte) T cell receptor (TCR)
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Summary:	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 , and 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Sid P. Kerkar, Boehringer Ingelheim, United States; Guo Fu, Xiamen University, China Edited by: Nick Gascoigne, National University of Singapore, Singapore These authors have contributed equally to this work ORCID: Andreas Dahl orcid.org/0000-0002-2668-8371 This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2019.02568