PMID- 34932366 OWN - NLM STAT- MEDLINE DCOM- 20220228 LR - 20230108 IS - 1535-3907 (Electronic) IS - 1535-3893 (Print) IS - 1535-3893 (Linking) VI - 21 IP - 1 DP - 2022 Jan 7 TI - HLA Allele-Specific Quantitative Profiling of Type 1 Diabetic B Lymphocyte Immunopeptidome. PG - 250-264 LID - 10.1021/acs.jproteome.1c00842 [doi] AB - Peptide ligands presented by human leukocyte antigen (HLA) molecules on the cell surface represent the immunopeptidome that could be utilized for identification of antigenic peptides for immunotherapy and prevention of autoimmune diseases. 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. FAU - Sudhir, Putty-Reddy AU - Sudhir PR AD - Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States. FAU - Lin, Tai-Du AU - Lin TD AD - Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States. FAU - Zhang, Qibin AU - Zhang Q AUID- ORCID: 0000-0002-6135-8706 AD - Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States. AD - Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27412, United States. LA - eng GR - R01 DK114345/DK/NIDDK NIH HHS/United States GR - R01 DK116731/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20211221 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Alleles MH - B-Lymphocytes MH - *Diabetes Mellitus, Type 1/metabolism MH - HLA Antigens MH - Histocompatibility Antigens Class I MH - Humans PMC - PMC8742597 MID - NIHMS1768692 OTO - NOTNLM OT - B lymphocytes OT - HLA allele OT - HLA ligandome OT - HLA-I OT - HLA-II OT - immunopeptidome OT - type 1 diabetes EDAT- 2021/12/22 06:00 MHDA- 2022/03/01 06:00 PMCR- 2023/01/07 CRDT- 2021/12/21 17:13 PHST- 2021/12/22 06:00 [pubmed] PHST- 2022/03/01 06:00 [medline] PHST- 2021/12/21 17:13 [entrez] PHST- 2023/01/07 00:00 [pmc-release] AID - 10.1021/acs.jproteome.1c00842 [doi] PST - ppublish SO - J Proteome Res. 2022 Jan 7;21(1):250-264. doi: 10.1021/acs.jproteome.1c00842. Epub 2021 Dec 21.