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Series GSE108413 Query DataSets for GSE108413
Status Public on Aug 02, 2018
Title Conventional and neo-antigenic peptides naturally processed and presented by beta cells are targeted by circulating naïve CD8+ T cells in type 1 diabetic and healthy donors
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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.
Overall design 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)
Contributor(s) Eizirik DL, Turatsinze J
Citation(s) 30078552, 33281748
Submission date Dec 21, 2017
Last update date Dec 08, 2020
Contact name Decio Laks Eizirik
Organization name Université Libre de Bruxelles
Department Faculté de Médecine
Lab ULB Center of Diabetes Research
Street address Route de Lennik 808
City Bruxelles
ZIP/Postal code 1070
Country Belgium
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (10)
GSM2897819 islet preparation 1 under control condition
GSM2897820 islet preparation 1 under cytokine treatment
GSM2897821 islet preparation 2 under control condition
BioProject PRJNA427190
SRA SRP127362

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Supplementary file Size Download File type/resource
GSE108413_RAW.tar 43.1 Mb (http)(custom) TAR (of GTF)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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