HLA Allele-Specific Quantitative Profiling of Type 1 Diabetic B Lymphocyte Immunopeptidome.

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Although T-cells are well-known key players in the destruction of pancreatic beta-cells in type 1 diabetes (T1D), increasing evidence points toward a role for B-cells in disease pathogenesis. However, as antigen presenting cells, little is known about the comprehensive immunopeptidome of B cells and their changes in the context of T1D. We performed HLA allele-specific quantitative immunopeptidomics using B lymphocytes derived from T1D patients and healthy controls. Hundreds of HLA-I and HLA-II immunopeptides were identified as differentially regulated in T1D per HLA allele for B cells sharing identical HLA alleles. The results were further validated using additional T1D and healthy B cells with partially overlapped HLA alleles. Differentially expressed immunopeptides were confirmed with targeted proteomics and for reactivity using known T-cell assays in the immune epitope database. Considering samples with identical HLA alleles are difficult to obtain for T1D and other similar HLA-restricted diseases, our work represents a viable approach to better understand HLA allele-specific antigen presentation and may facilitate identification of immunopeptides for therapeutic applications in autoimmune diseases. Data are available via ProteomeXchange with identifier PXD026184.", "claims": [{"id": "claim-method", "statement": "The t-test with both sides and 250 randomizations was adapted for significance analysis with S0 of 0.1 and FDR cutoff 0.05 or 0.01.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34932366", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "The t-test with both sides and 250 randomizations was adapted for significance analysis with S0 of 0.1 and FDR cutoff 0.05 or 0.01."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available via ProteomeXchange with identifier PXD026184.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34932366", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available via ProteomeXchange with identifier PXD026184."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Hundreds of HLA-I and HLA-II immunopeptides were identified as differentially regulated in T1D per HLA allele for B cells sharing identical HLA alleles.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34932366", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Hundreds of HLA-I and HLA-II immunopeptides were identified as differentially regulated in T1D per HLA allele for B cells sharing identical HLA alleles."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Hundreds of HLA-I and HLA-II immunopeptides were identified as differentially regulated in T1D per HLA allele for B cells sharing identical HLA alleles.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34932366"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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