PMID- 38043703 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240206 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 23 IP - 1 DP - 2024 Jan TI - IMBAS-MS Discovers Organ-Specific HLA Peptide Patterns in Plasma. PG - 100689 LID - S1535-9476(23)00200-1 [pii] LID - 10.1016/j.mcpro.2023.100689 [doi] LID - 100689 AB - Distinction of non-self from self is the major task of the immune system. Immunopeptidomics studies the peptide repertoire presented by the human leukocyte antigen (HLA) protein, usually on tissues. However, HLA peptides are also bound to plasma soluble HLA (sHLA), but little is known about their origin and potential for biomarker discovery in this readily available biofluid. Currently, immunopeptidomics is hampered by complex workflows and limited sensitivity, typically requiring several mL of plasma. Here, we take advantage of recent improvements in the throughput and sensitivity of mass spectrometry (MS)-based proteomics to develop a highly sensitive, automated, and economical workflow for HLA peptide analysis, termed Immunopeptidomics by Biotinylated Antibodies and Streptavidin (IMBAS). IMBAS-MS quantifies more than 5000 HLA class I peptides from only 200 mul of plasma, in just 30 min. Our technology revealed that the plasma immunopeptidome of healthy donors is remarkably stable throughout the year and strongly correlated between individuals with overlapping HLA types. Immunopeptides originating from diverse tissues, including the brain, are proportionately represented. We conclude that sHLAs are a promising avenue for immunology and potentially for precision oncology. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Wahle, Maria AU - Wahle M AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. FAU - Thielert, Marvin AU - Thielert M AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. FAU - Zwiebel, Maximilian AU - Zwiebel M AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. FAU - Skowronek, Patricia AU - Skowronek P AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. FAU - Zeng, Wen-Feng AU - Zeng WF AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. FAU - Mann, Matthias AU - Mann M AD - Department Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. Electronic address: mmann@biochem.mpg.de. LA - eng PT - Journal Article DEP - 20231201 PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 RN - 9013-20-1 (Streptavidin) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Peptides) RN - 0 (Antibodies) SB - IM MH - Humans MH - Streptavidin MH - *Neoplasms MH - Precision Medicine MH - Histocompatibility Antigens Class I/metabolism MH - HLA Antigens MH - Histocompatibility Antigens Class II MH - Peptides/metabolism MH - Mass Spectrometry MH - Antibodies PMC - PMC10765297 OTO - NOTNLM OT - HLA OT - IMBAS-MS OT - immunopeptidomics OT - plasma immunopeptidomics OT - sHLA COIS- Conflict of interest M. M. is an indirect investor in Evosep Biosystems. All other authors declare that they have no conflicts of interest with the contents of this article. EDAT- 2023/12/04 00:42 MHDA- 2024/01/29 06:43 PMCR- 2023/12/01 CRDT- 2023/12/03 19:27 PHST- 2023/08/22 00:00 [received] PHST- 2023/11/24 00:00 [revised] PHST- 2023/11/28 00:00 [accepted] PHST- 2024/01/29 06:43 [medline] PHST- 2023/12/04 00:42 [pubmed] PHST- 2023/12/03 19:27 [entrez] PHST- 2023/12/01 00:00 [pmc-release] AID - S1535-9476(23)00200-1 [pii] AID - 100689 [pii] AID - 10.1016/j.mcpro.2023.100689 [doi] PST - ppublish SO - Mol Cell Proteomics. 2024 Jan;23(1):100689. doi: 10.1016/j.mcpro.2023.100689. Epub 2023 Dec 1.