RESUMEN
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.
Asunto(s)
Antígenos/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Perfilación de la Expresión Génica , Análisis de la Célula Individual , Presentación de Antígeno/inmunología , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Autoantígenos/inmunología , Perfilación de la Expresión Génica/métodos , Antígenos de Histocompatibilidad Clase I/química , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Péptidos/inmunología , Análisis de la Célula Individual/métodos , Proteínas de la Matriz Viral/química , Proteínas de la Matriz Viral/inmunologíaRESUMEN
Those of us with chronic Lyme disease are not at all confused, as suggested by Sigal and Hassett (2002). We know from years of experience that we have real, specific symptoms that are usually painful and disabling and include severe headaches, crippling arthritis, and heart palpitations, which lead to serious heart disease. Many of us know that our symptoms are kept in check while we are on antibiotics, but they painfully reappear when the antibiotics are withdrawn. Just because the medical community cannot detect a specific causative bacterium and managed health care companies want to maximize profits doesn't mean that those of us afflicted with this terrible condition are delusional and not truly benefiting from antibiotic treatment. We are not all crazy; we are sick and we should not be required to prove it to get medical care.