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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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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 |
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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 |
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