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Strong basal/tonic TCR signals are associated with chromatin accessibility changes in naive CD4+ T cells

ABSTRACT: Strong basal/tonic TCR signals are associated with chromatin accessibility changes in naive CD4+ T cells

PROVIDER: PRJNA849017 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19647900_1.fastq.gz	Fastqsanger.gz
	SRR19647900_2.fastq.gz	Fastqsanger.gz
	SRR19647901_1.fastq.gz	Fastqsanger.gz
	SRR19647901_2.fastq.gz	Fastqsanger.gz
	SRR19647902_1.fastq.gz	Fastqsanger.gz

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Strong basal/tonic TCR signals are associated with gene expression changes in naive CD4+ T cells

Project description:Naïve T cells constantly experience TCR signals in response to self-peptides presented by MHC (pMHC) in vivo. The intensity of these basal or tonic TCR signals can be indirectly read out by expression of surrogate markers of tonic TCR signaling, including the Nur77-GFP transgene and Ly6c. The strength of tonic TCR signaling varies broadly across the naïve CD4+ T cell population and is correlated with functional heterogeneity.Cells that experience the most basal TCR signaling (Nur77-GFP hi, Ly6c lo) are hyporesponsive to peptide-MHC stimulation. Here we examine whether tonic TCR stimulation is associated with differences in mRNA expression.

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Strong basal/tonic TCR signals are associated with chromatin accessibility changes in naive CD4+ T cells

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Strong basal/tonic TCR signals are associated with transcriptional and epigenetic changes in naive CD4+ T cells

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Project description:The strength of the T cell receptor interaction with self-ligands affects antigen-specific immune responses. However, the precise role, functional relationship, and underlying mechanisms have not been elucidated completely. Here, we demonstrate that naive CD8+ T cells with relatively high self-reactivity are phenotypically heterogeneous owing to varied responses to type I interferon (T1IFN), resulting in three distinct subsets, CD5loLy6C–, CD5hiLy6C–, and CD5hiLy6C+ cells. CD5hiLy6C+ cells differ from CD5loLy6C– and CD5hiLy6C– cells in their gene expression profiles and functional properties. Moreover, CD5hiLy6C+ cells demonstrate more extensive antigen-specific expansion upon viral infection, with enhanced differentiation into terminal effector cells and reduced memory cell generation. Such unique features of CD5hiLy6C+ cells are imprinted in a steady-state and observed even for those of monoclonal CD8+ T cell populations in a T1IFN dependent fashion. These findings demonstrate that self-reactivity shapes the functional diversity of naive CD8+ T cells by co-opting tonic T1IFN signaling.

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