Gene Expression-Based Identification of Antigen-Responsive CD8+ T Cells on a Single-Cell Level release_y7gc4ze7kjaxrjf54oty4wjeiy

by Yannick F. Fuchs, Virag Sharma, Anne Eugster, Gloria Kraus, Robert Morgenstern, Andreas Dahl, Susanne Reinhardt, Andreas Petzold, Annett Lindner, Doreen Löbel, Ezio Bonifacio

Published in Frontiers in Immunology by Frontiers Media SA.

2019   Volume 10, p2568

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.
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