AUTHOR=Fuchs Yannick F. , Sharma Virag , Eugster Anne , Kraus Gloria , Morgenstern Robert , Dahl Andreas , Reinhardt Susanne , Petzold Andreas , Lindner Annett , Löbel Doreen , Bonifacio Ezio TITLE=Gene Expression-Based Identification of Antigen-Responsive CD8+ T Cells on a Single-Cell Level JOURNAL=Frontiers in Immunology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02568 DOI=10.3389/fimmu.2019.02568 ISSN=1664-3224 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.