Identification of naturally processed mumps virus epitopes by mass spectrometry: Confirmation of multiple CD8+ T cell responses in mumps patients.

Abstract

BACKGROUND\nThe 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. Recently, 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.\n\n\nMETHODS\nPeptides were eluted from 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.\n\n\nRESULTS\nHere we identified a broad landscape of 83 CD8+ T cell epitopes of MuV, of which 41 were confirmed based on synthetic peptide standards. For six epitopes we showed induction of an HLA-A*02-restriced CD8+ T cell response. Moreover, robust T cell responses against five selected MuV epitopes could be detected in all tested mumps patients using peptide/HLA-A*02:01 dextramers.\n\n\nCONCLUSION\nThe identified CD8+ T cell epitopes will help to further characterize MuV-specific T cell immunity following natural MuV infection or vaccination. These MuV epitopes may provide clues for a better understanding of, and possibly for preventing, mumps vaccine failure.