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- Title
Identification of Naturally Processed Mumps Virus Epitopes by Mass Spectrometry: Confirmation of Multiple CD8+ T-Cell Responses in Mumps Patients.
- Authors
Wit, Jelle de; Emmelot, Maarten E; Meiring, Hugo; Brink, Jacqueline A M van Gaans-van den; Els, Cécile A C M van; Kaaijk, Patricia; de Wit, Jelle; van Gaans-van den Brink, Jacqueline A M; van Els, Cécile A C M
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
MUMPS; T cell receptors; MASS spectrometry; HLA histocompatibility antigens; EPITOPES; T cells; RESEARCH; HLA-B27 antigen; CELL culture; LIQUID chromatography; RESEARCH methodology; EVALUATION research; MEDICAL cooperation; INTERFERONS; COMPARATIVE studies; GENOTYPES; PARAMYXOVIRUSES; ANTIGENS; PEPTIDES
- Publication
Journal of Infectious Diseases, 2020, Vol 221, Issue 3, p474
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz480