|
| 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.
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| |
|
| 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 |
| GSM2897822 |
islet preparation 2 under cytokine treatment |
| GSM2897823 |
islet preparation 3 under control condition |
| GSM2897824 |
islet preparation 3 under cytokine treatment |
| GSM2897825 |
islet preparation 4 under control condition |
| GSM2897826 |
islet preparation 4 under cytokine treatment |
| GSM2897827 |
islet preparation 5 under control condition |
| GSM2897828 |
islet preparation 5 under cytokine treatment |
|
| Relations |
| BioProject |
PRJNA427190 |
| SRA |
SRP127362 |
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