Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells
Abstract Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell e...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-00023-0 |
| _version_ | 1818938066979520512 |
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| author | Margot Miranda-Katz John J. Erickson Jie Lan Alwyn Ecker Yu Zhang Sebastian Joyce John V. Williams |
| author_facet | Margot Miranda-Katz John J. Erickson Jie Lan Alwyn Ecker Yu Zhang Sebastian Joyce John V. Williams |
| author_sort | Margot Miranda-Katz |
| collection | DOAJ |
| description | Abstract Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design. |
| first_indexed | 2024-12-20T06:01:57Z |
| format | Article |
| id | doaj.art-db3aa5a211854328ac4fcd0e108f8cda |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-20T06:01:57Z |
| publishDate | 2021-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-db3aa5a211854328ac4fcd0e108f8cda2022-12-21T19:50:53ZengNature PortfolioScientific Reports2045-23222021-10-0111111010.1038/s41598-021-00023-0Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cellsMargot Miranda-Katz0John J. Erickson1Jie Lan2Alwyn Ecker3Yu Zhang4Sebastian Joyce5John V. Williams6Department of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of PittsburghDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of MedicineDepartment of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of PittsburghDepartment of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of PittsburghDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of MedicineDepartment of Pediatrics, University of Pittsburgh School of Medicine, UPMC Children’s Hospital of PittsburghAbstract Human metapneumovirus (HMPV) is a leading cause of acute lower respiratory tract illness in children and adults. Repeated infections are common and can be severe in young, elderly, and immunocompromised persons due to short-lived protective humoral immunity. In turn, few protective T cell epitopes have been identified in humans. Thus, we infected transgenic mice expressing the common human HLA MHC-I allele B*07:02 (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8+ T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M195–203 (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8+ T cells migrated to lungs and spleen of HMPV-immune mice. Immunization with pooled HLA-B7-restricted peptides reduced viral titer and protected mice from virulent infection. Finally, we confirmed that CD8+ T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8+ T cells in humans and help to inform future HMPV vaccine design.https://doi.org/10.1038/s41598-021-00023-0 |
| spellingShingle | Margot Miranda-Katz John J. Erickson Jie Lan Alwyn Ecker Yu Zhang Sebastian Joyce John V. Williams Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells Scientific Reports |
| title | Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells |
| title_full | Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells |
| title_fullStr | Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells |
| title_full_unstemmed | Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells |
| title_short | Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells |
| title_sort | novel hla b7 restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human cd8 t cells |
| url | https://doi.org/10.1038/s41598-021-00023-0 |
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