Abstract
Mumps is nowadays re-emerging despite vaccination. The contribution of T cell immunity to protection against mumps has not been clearly defined. Previously, we described a set of 41 peptides that were eluted from human leukocyte antigen (HLA) class I molecules of mumps virus (MuV)-infected cells. Here, we confirmed immunogenicity of five novel HLA-B*07:02- and HLA-A*01:01-restricted MuV T cell epitopes from this set of peptides. High frequencies of T cells against these five MuV epitopes could be detected ex vivo in all tested mumps patients. Moreover, these epitope-specific T cells derived from mumps patients displayed strong cytotoxic activity. In contrast, only marginal T cell responses against these novel MuV epitopes could be detected in recently vaccinated persons, corroborating earlier findings. Identifying which MuV epitopes are dominantly targeted in the mumps-specific CD8+ T- response is an important step towards better understanding in the discrepancies between natural infection or vaccination-induced cell-mediated immune protection.
Highlights
We describe five novel human leukocyte antigen (HLA)-B*07:02and HLA-A*01:01-restricted mumps virus (MuV) epitopes that reveal for the first time robust ongoing cytotoxic T cell responses in all mumps patients tested, with only low frequencies of epitope-specific T cells in recently vaccinated persons
Selected epitopes were tested for their capacity to recall a specific T cell response, by using expanded CD8 + T-effector cells isolated from three HLA-B*07:02 positive and three HLA-A*01:01 positive mumps patients (Fig. 1)
YSDPNNHEVY and not its post-translationally modified deamination variant, YSDPNDHEVY, was selected because it was more abundantly presented based on elution from MHC-I molecules from MuV-infected c ells[16] and had a better predictive binding to HLA-A*01:01 (Fig. 1)
Summary
A set of 41 unique viral peptides was eluted from HLA class I molecules of MuV-infected cells (typing: HLA-A*01:01, A*02:01, B*07:02, B*40:01, C*03:04, C*07:02) and characterized by mass spectrometry. From this panel, we confirmed the first six HLA-A*02:01-restricted MuV T cell epitopes to be able to induce a T-cell response[16]. We describe five novel HLA-B*07:02and HLA-A*01:01-restricted MuV epitopes that reveal for the first time robust ongoing cytotoxic T cell responses in all mumps patients tested, with only low frequencies of epitope-specific T cells in recently vaccinated persons
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