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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
E-mail(s) deizirik@ulb.ac.be
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
Relations
BioProject PRJNA427190
SRA SRP127362

Download family Format
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Series Matrix File(s) TXTHelp

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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