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GROUP | CONDITION | SAMPLES |
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Human islets of Langerhans |
GSM2897822 GSM2897826
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GSM2897819 GSM2897823 GSM2897827
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Submission Date: Dec 21, 2017
Summary: Human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes. However, their target epitopes have not been demonstrated to be naturally processed and presented by β cells. We therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Preproinsulin yielded multiple previously described HLA-A2-restricted epitopes. Secretogranin V (SCG5/7B2), proconvertase-2, urocortin-3 and the insulin gene enhancer protein ISL-1 were identified as novel β-cell antigens, which were processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative mRNA splice isoform (SCG5-009) and from an islet amyloid polypeptide transpeptidation product. This first description of the β-cell HLA peptidome opens new avenues to understand the antigen processing pathways employed by β cells and provides a valuable tool for developing T-cell biomarkers and tolerogenic vaccination strategies.
GEO Accession ID: GSE108413
PMID: 30078552
Submission Date: Dec 21, 2017
Summary: Human CD8+ T cells are the final mediators of autoimmune β-cell destruction in type 1 diabetes. However, their target epitopes have not been demonstrated to be naturally processed and presented by β cells. We therefore performed an epitope discovery study combining HLA Class I peptidomics and transcriptomics strategies. Inflammatory cytokines increased β-cell peptide presentation in vitro, paralleling upregulation of HLA Class I expression. Peptide sources included known β-cell antigens and several insulin granule proteins. Preproinsulin yielded multiple previously described HLA-A2-restricted epitopes. Secretogranin V (SCG5/7B2), proconvertase-2, urocortin-3 and the insulin gene enhancer protein ISL-1 were identified as novel β-cell antigens, which were processed into HLA-A2-restricted epitopes recognized by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors. HLA-A2-bound neo-epitopes were also represented and originated from an alternative mRNA splice isoform (SCG5-009) and from an islet amyloid polypeptide transpeptidation product. This first description of the β-cell HLA peptidome opens new avenues to understand the antigen processing pathways employed by β cells and provides a valuable tool for developing T-cell biomarkers and tolerogenic vaccination strategies.
GEO Accession ID: GSE108413
PMID: 30078552
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This pipeline enables you to analyze and visualize your bulk RNA sequencing datasets with an array of downstream analysis and visualization tools. The pipeline includes: PCA analysis, Clustergrammer interactive heatmap, library size analysis, differential gene expression analysis, enrichment analysis, and L1000 small molecule search.