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

• Published in: Frontiers in immunology Vol. 10; p. 2568
• Main Authors: Fuchs, Yannick F, Sharma, Virag, Eugster, Anne, Kraus, Gloria, Morgenstern, Robert, Dahl, Andreas, Reinhardt, Susanne, Petzold, Andreas, Lindner, Annett, Löbel, Doreen, Bonifacio, Ezio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 06-11-2019
• Subjects: antigen-responsive; CD8+ T cells; CTL (cytotoxic T lymphocyte); gene-expression analysis; Immunology; influenza matrix protein; single-cell; CD8+ T cells; CMV pp65; antigen-responsive; single-cell; gene-expression analysis; influenza matrix protein; CTL (cytotoxic T lymphocyte); T cell receptor (TCR)
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2019.02568

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
, and
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.