PMID- 31560392 OWN - NLM STAT- MEDLINE DCOM- 20200921 LR - 20200921 IS - 1537-6613 (Electronic) IS - 0022-1899 (Linking) VI - 221 IP - 3 DP - 2020 Jan 14 TI - Identification of Naturally Processed Mumps Virus Epitopes by Mass Spectrometry: Confirmation of Multiple CD8+ T-Cell Responses in Mumps Patients. PG - 474-482 LID - 10.1093/infdis/jiz480 [doi] AB - BACKGROUND: The re-emergence of mumps among vaccinated young adults has become a global issue. Besides waning of antibody responses, suboptimal induction of T-cell responses may reduce protection. In a recent study, we observed a dominant polyfunctional CD8+ T-cell response after natural mumps virus (MuV) infection that was not present after vaccination. Unraveling the MuV epitope repertoire can provide insight in the specificity, functionality, and breadth of the T-cell response against MuV. METHODS: Peptides were eluted from human leukocyte antigen (HLA) class I molecules of MuV-infected cells and characterized by advanced mass spectrometry. Selected identified MuV peptides were tested for in vitro and ex vivo immunogenicity. RESULTS: In this study, we identified a broad landscape of 83 CD8+ T-cell epitopes of MuV, 41 of which were confirmed based on synthetic peptide standards. For 6 epitopes, we showed induction of an HLA-A*02-restriced CD8+ T-cell response. Moreover, robust T-cell responses against 5 selected MuV epitopes could be detected in all tested mumps patients using peptide/HLA-A*02:01 dextramers. CONCLUSIONS: The identified CD8+ T-cell epitopes will help to further characterize MuV-specific T-cell immunity after natural MuV infection or vaccination. These MuV epitopes may provide clues for a better understanding of, and possibly for preventing, mumps vaccine failure.We identified for the first time 41 mumps virus (MuV)-specific HLA-A*02 epitopes. For 6 epitopes, CD8+ T-cell responses were confirmed in T cells derived from several mumps cases, and MuV-specific CD8+ T cells could be identified by peptide/dextramer staining. CI - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. FAU - de Wit, Jelle AU - de Wit J AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. FAU - Emmelot, Maarten E AU - Emmelot ME AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. FAU - Meiring, Hugo AU - Meiring H AD - Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands. FAU - van Gaans-van den Brink, Jacqueline A M AU - van Gaans-van den Brink JAM AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. FAU - van Els, Cecile A C M AU - van Els CACM AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. FAU - Kaaijk, Patricia AU - Kaaijk P AD - Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A*02 antigen) RN - 0 (HLA-A2 Antigen) RN - 0 (IFNG protein, human) RN - 0 (Peptides) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - CD8-Positive T-Lymphocytes/*immunology MH - Cells, Cultured MH - Chromatography, Reverse-Phase/methods MH - Epitopes, T-Lymphocyte/chemistry/*immunology MH - Genotype MH - HLA-A2 Antigen/chemistry/immunology MH - Humans MH - Interferon-gamma/biosynthesis MH - Mumps/*immunology/pathology/virology MH - Mumps virus/genetics/*immunology MH - Peptides/chemistry/immunology MH - Tandem Mass Spectrometry/*methods MH - Young Adult OTO - NOTNLM OT - MHC class I OT - MMR OT - T-cell immunity OT - immunopeptidome OT - mumps infection EDAT- 2019/09/29 06:00 MHDA- 2020/09/22 06:00 CRDT- 2019/09/28 06:00 PHST- 2019/07/22 00:00 [received] PHST- 2019/09/19 00:00 [accepted] PHST- 2019/09/29 06:00 [pubmed] PHST- 2020/09/22 06:00 [medline] PHST- 2019/09/28 06:00 [entrez] AID - 5575092 [pii] AID - 10.1093/infdis/jiz480 [doi] PST - ppublish SO - J Infect Dis. 2020 Jan 14;221(3):474-482. doi: 10.1093/infdis/jiz480.