Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Fuchs, Yannick F., Sharma, Virag, Eugster, Anne, Kraus, Gloria, Morgenstern, Robert, Dahl, Andreas, Reinhardt, Susanne, Petzold, Andreas, Lindner, Annett, Löbel, Doreen, Bonifacio, Ezio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851025/
https://www.ncbi.nlm.nih.gov/pubmed/31781096
http://dx.doi.org/10.3389/fimmu.2019.02568
_version_ 1783469551048982528
author Fuchs, Yannick F.
Sharma, Virag
Eugster, Anne
Kraus, Gloria
Morgenstern, Robert
Dahl, Andreas
Reinhardt, Susanne
Petzold, Andreas
Lindner, Annett
Löbel, Doreen
Bonifacio, Ezio
author_facet Fuchs, Yannick F.
Sharma, Virag
Eugster, Anne
Kraus, Gloria
Morgenstern, Robert
Dahl, Andreas
Reinhardt, Susanne
Petzold, Andreas
Lindner, Annett
Löbel, Doreen
Bonifacio, Ezio
author_sort Fuchs, Yannick F.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6851025
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68510252019-11-28 Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level Fuchs, Yannick F. Sharma, Virag Eugster, Anne Kraus, Gloria Morgenstern, Robert Dahl, Andreas Reinhardt, Susanne Petzold, Andreas Lindner, Annett Löbel, Doreen Bonifacio, Ezio Front Immunol Immunology 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. Frontiers Media S.A. 2019-11-06 /pmc/articles/PMC6851025/ /pubmed/31781096 http://dx.doi.org/10.3389/fimmu.2019.02568 Text en Copyright © 2019 Fuchs, Sharma, Eugster, Kraus, Morgenstern, Dahl, Reinhardt, Petzold, Lindner, Löbel and Bonifacio. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fuchs, Yannick F.
Sharma, Virag
Eugster, Anne
Kraus, Gloria
Morgenstern, Robert
Dahl, Andreas
Reinhardt, Susanne
Petzold, Andreas
Lindner, Annett
Löbel, Doreen
Bonifacio, Ezio
Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title_full Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title_fullStr Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title_full_unstemmed Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title_short Gene Expression-Based Identification of Antigen-Responsive CD8(+) T Cells on a Single-Cell Level
title_sort gene expression-based identification of antigen-responsive cd8(+) t cells on a single-cell level
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851025/
https://www.ncbi.nlm.nih.gov/pubmed/31781096
http://dx.doi.org/10.3389/fimmu.2019.02568
work_keys_str_mv AT fuchsyannickf geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT sharmavirag geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT eugsteranne geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT krausgloria geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT morgensternrobert geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT dahlandreas geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT reinhardtsusanne geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT petzoldandreas geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT lindnerannett geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT lobeldoreen geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel
AT bonifacioezio geneexpressionbasedidentificationofantigenresponsivecd8tcellsonasinglecelllevel