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Germline-like TCR alpha chains shared between autoreactive T cells in blood and pancreas

ABSTRACT: Germline-like TCR alpha chains shared between autoreactive T cells in blood and pancreas

PROVIDER: PRJNA1079752 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27921800_1.fastq.gz	Fastqsanger.gz
	SRR27921800_2.fastq.gz	Fastqsanger.gz
	SRR27921900_1.fastq.gz	Fastqsanger.gz
	SRR27921900_2.fastq.gz	Fastqsanger.gz
	SRR27922000_1.fastq.gz	Fastqsanger.gz

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Germline-like TCR alpha chains shared between autoreactive T cells in blood and pancreas [dataset2]

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Identification of shared TCR sequences from T cells in human breast cancer using emulsion RT-PCR

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Self-reactive germline-like TCR alpha chains shared between blood and pancreas.

Project description:Human islet antigen reactive CD4 + memory T cells (IAR T cells) from peripheral blood have been studied extensively for their role in the pathogenesis of autoimmune type 1 diabetes (T1D). However, IAR T cells are rare, and it remains poorly understood how they affect T1D progression in the pancreas. Using single cell RNA-sequencing coupled with a multiplexed activation induced marker (AIM) enrichment assay, we identified paired TCR alpha/beta (TRA/TRB) T cell receptors (TCRs) in IAR T cells from the blood of healthy, at-risk, new onset, and established T1D donors. Using TCR sequences as barcodes, we measured infiltration of IAR T cells from blood into pancreas of organ donors with and without T1D. We detected extensive TCR sharing between IAR T cells from peripheral blood and pancreatic infiltrating T cells (PIT), with perfectly matched or single mismatched TRA junctions and J gene regions, comprising ~ 34% of unique IAR TCRs. PIT-matching IAR T cells had public TRA chains that showed increased use of germline-encoded residues in epitope engagement and a propensity for cross-reactivity. The link with T cells in the pancreas implicates autoreactive IAR T cells with shared TRA junctions and increased levels in blood with the prediabetic and new onset phases of T1D progression.

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