PMID- 33933681 OWN - NLM STAT- MEDLINE DCOM- 20220321 LR - 20220321 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 20 DP - 2021 TI - HLA Class II Presentation Is Specifically Altered at Elevated Temperatures in the B-Lymphoblastic Cell Line JY. PG - 100089 LID - S1535-9476(21)00062-1 [pii] LID - 10.1016/j.mcpro.2021.100089 [doi] LID - 100089 AB - Human leukocyte antigen (HLA) molecules play critical roles in our adaptive immune system by signaling a cell's health status to the immune system, through presentation of small peptides. Understanding HLA biology is important because of its prominent role in autoimmune diseases and cancer immunotherapy. Although both the HLA class I and class II antigen processing and presentation pathways have been studied extensively, the fundamental rules in HLA class II antigen presentation still remain less understood. To clarify the mechanistic and adaptive differences between the HLA systems, we challenged a B lymphoblastic cell line (JY), widely used as model system in studying antigen presentation, with a high temperature treatment to mimic a "fever-like state", representing one of the most common physiological responses to infection. In the absence of real invading pathogenic peptides to present, we could focus on delineating the intrinsic HLA pathway adaptations in response to high temperature in this particular cell line. Following a three-pronged approach, we performed quantitative analyses of the proteome, the HLA class I ligandome, as well as the HLA class II ligandome. The data reveals that elevated temperature may already prepare these cells for an immune-like response through increased HLA class II presentation capacity and specific release of, from the invariant chain originating, CLIP peptides. Interestingly, at high temperature, prominent changes in the composition of the CLIP repertoire were observed, with enrichment of peptides containing C-terminal extensions beyond the CLIP-core region. Collectively, these illustrate intriguing temperature sensitive adaptations in this B cell line. CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Demmers, Laura C AU - Demmers LC AD - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Netherlands Proteomics Centre, Utrecht, Netherlands. FAU - Wu, Wei AU - Wu W AD - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Netherlands Proteomics Centre, Utrecht, Netherlands. FAU - Heck, Albert J R AU - Heck AJR AD - Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands; Netherlands Proteomics Centre, Utrecht, Netherlands. Electronic address: a.j.r.heck@uu.nl. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210429 PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Ligands) RN - 0 (Proteome) SB - IM MH - Antigen Presentation MH - B-Lymphocytes/*immunology MH - Cell Line MH - Fever/*immunology MH - Histocompatibility Antigens Class I/immunology MH - Histocompatibility Antigens Class II/*immunology MH - Humans MH - Ligands MH - Proteome MH - Temperature PMC - PMC8724904 OTO - NOTNLM OT - CLIP peptide cluster OT - HLA class I peptide presentation OT - HLA class II peptide presentation OT - HLA peptide processing OT - immunopeptidomics OT - immunoproteomics OT - invariant chain OT - temperature-induced adaptations COIS- Conflict of interest The authors declare no competing interests. EDAT- 2021/05/03 06:00 MHDA- 2022/03/22 06:00 PMCR- 2021/04/29 CRDT- 2021/05/02 20:46 PHST- 2020/12/19 00:00 [received] PHST- 2021/03/25 00:00 [revised] PHST- 2021/04/13 00:00 [accepted] PHST- 2021/05/03 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/05/02 20:46 [entrez] PHST- 2021/04/29 00:00 [pmc-release] AID - S1535-9476(21)00062-1 [pii] AID - 100089 [pii] AID - 10.1016/j.mcpro.2021.100089 [doi] PST - ppublish SO - Mol Cell Proteomics. 2021;20:100089. doi: 10.1016/j.mcpro.2021.100089. Epub 2021 Apr 29.