Gene Expression-Based Identification of Antigen-Responsive CD8+ T Cells on a Single-Cell Level
| Autor: | Yannick F. Fuchs, Virag Sharma, Anne Eugster, Gloria Kraus, Robert Morgenstern, Andreas Dahl, Susanne Reinhardt, Andreas Petzold, Annett Lindner, Doreen Löbel, Ezio Bonifacio |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Immunology Antigen presentation Antigen-Presenting Cells CD8-Positive T-Lymphocytes Biology CD8+ T cells gene-expression analysis Autoantigens Viral Matrix Proteins 03 medical and health sciences 0302 clinical medicine Antigen Gene expression Humans Immunology and Allergy Cytotoxic T cell T cell receptor (TCR) Antigens Original Research Antigen Presentation CMV pp65 Gene Expression Profiling CTL (cytotoxic T lymphocyte) Histocompatibility Antigens Class I T-cell receptor single-cell Acquired immune system Molecular biology 030104 developmental biology Cd8(+) T Cells Single-cell Antigen-responsive Gene-expression Analysis Ctl (cytotoxic T Lymphocyte) Influenza Matrix Protein Cmv Pp65 T Cell Receptor (tcr) antigen-responsive influenza matrix protein Single-Cell Analysis Peptides lcsh:RC581-607 CD8 030215 immunology XCL1 |
| Zdroj: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology Front. Immunol. 10:2568 (2019) |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2019.02568 |
| Popis: | 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-labelled 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.One-sentence summaryIdentification of genes, gene sets, and development of a machine learning-based classifier that distinguishes antigen-responsive CD8+ T cells on a single-cell level. |
| Databáze: | OpenAIRE |
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