PMID- 37709257 OWN - NLM STAT- Publisher LR - 20231021 IS - 1535-9484 (Electronic) IS - 1535-9476 (Print) IS - 1535-9476 (Linking) VI - 22 IP - 10 DP - 2023 Oct TI - Integrated Immunopeptidomics and Proteomics Study of SARS-CoV-2-Infected Calu-3 Cells Reveals Dynamic Changes in Allele-specific HLA Abundance and Antigen Presentation. PG - 100645 LID - S1535-9476(23)00156-1 [pii] LID - 10.1016/j.mcpro.2023.100645 [doi] LID - 100645 AB - We present an integrated immunopeptidomics and proteomics study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection to comprehensively decipher the changes in host cells in response to viral infection. Immunopeptidomics analysis identified viral antigens presented by host cells through both class I and class II MHC system for recognition by the adaptive immune system. The host proteome changes were characterized by quantitative proteomics and glycoproteomics and from these data, the activation of toll-like receptor 3-interferon pathway was identified. Glycosylation analysis of human leukocyte antigen (HLA) proteins from the elution and flow-through of immunoprecipitation revealed that SARS-CoV-2 infection changed the glycosylation pattern of certain HLA alleles with different HLA alleles, showing distinct dynamic changes in relative abundance. The difference in the glycosylation and abundance of HLA alleles changed the number of strong binding antigens each allele presented, suggesting the impact of SARS-CoV-2 infection on antigen presentation is allele-specific. These results could be further exploited to explain the imbalanced response from innate and adaptive immune system in coronavirus disease 2019 cases, which would be helpful for the development of therapeutics and vaccine for coronavirus disease 2019 and preparation for future pandemic. CI - Crown Copyright (c) 2023. Published by Elsevier Inc. All rights reserved. FAU - Chen, Rui AU - Chen R AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. Electronic address: Rui.Chen@nrc-cnrc.gc.ca. FAU - Fulton, Kelly M AU - Fulton KM AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. FAU - Tran, Anh AU - Tran A AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. FAU - Duque, Diana AU - Duque D AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. FAU - Kovalchik, Kevin AU - Kovalchik K AD - CHU Sainte-Justine Research Center, Montreal, Quebec, Canada. FAU - Caron, Etienne AU - Caron E AD - CHU Sainte-Justine Research Center, Montreal, Quebec, Canada; Department of Pathology and Cellular Biology, Faculty of Medicine, Universite de Montreal, Quebec, Canada. FAU - Twine, Susan M AU - Twine SM AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. FAU - Li, Jianjun AU - Li J AD - Human Health Therapeutics Research Centre, National Research Council Canada, Ottawa, Ontario, Canada. Electronic address: Jianjun.Li@nrc-cnrc.gc.ca. LA - eng PT - Journal Article DEP - 20230913 PL - United States TA - Mol Cell Proteomics JT - Molecular & cellular proteomics : MCP JID - 101125647 SB - IM PMC - PMC10580047 COIS- Conflict of interest The authors declare no competing interests. EDAT- 2023/09/15 00:42 MHDA- 2023/09/15 00:42 PMCR- 2023/09/13 CRDT- 2023/09/14 19:19 PHST- 2022/10/04 00:00 [received] PHST- 2023/08/29 00:00 [revised] PHST- 2023/09/11 00:00 [accepted] PHST- 2023/09/15 00:42 [pubmed] PHST- 2023/09/15 00:42 [medline] PHST- 2023/09/14 19:19 [entrez] PHST- 2023/09/13 00:00 [pmc-release] AID - S1535-9476(23)00156-1 [pii] AID - 100645 [pii] AID - 10.1016/j.mcpro.2023.100645 [doi] PST - ppublish SO - Mol Cell Proteomics. 2023 Oct;22(10):100645. doi: 10.1016/j.mcpro.2023.100645. Epub 2023 Sep 13.