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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 <jats:italic>B*07:02<\/jats:italic> (HLA-B7) with HMPV and screened a robust library of overlapping and computationally predicted HLA-B7 binding peptides. Six HLA-B7-restricted CD8<jats:sup>+<\/jats:sup> T cell epitopes were identified using ELISPOT screening in the F, M, and N proteins, with M<jats:sub>195\u2013203<\/jats:sub> (M195) eliciting the strongest responses. MHC-tetramer flow cytometric staining confirmed HLA-B7 epitope-specific CD8<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells from HLA-B7 positive humans also recognize the identified epitopes. These results enable identification of HMPV-specific CD8<jats:sup>+<\/jats:sup> T cells in humans and help to inform future HMPV vaccine design.<\/jats:p>","DOI":"10.1038\/s41598-021-00023-0","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T10:04:42Z","timestamp":1634810682000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel HLA-B7-restricted human metapneumovirus epitopes enhance viral clearance in mice and are recognized by human CD8+ T cells"],"prefix":"10.1038","volume":"11","author":[{"given":"Margot","family":"Miranda-Katz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Erickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwyn","family":"Ecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Joyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John V.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"23_CR1","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/89098","volume":"7","author":"BG van den Hoogen","year":"2001","unstructured":"van den Hoogen, B. 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