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In murine models of LCMV infection, CD8<jats:sup>+<\/jats:sup>T cells play a primary role in providing protective immunity, and there is evidence that cellular immunity may also be important in related arenavirus infections in humans. For this reason, we sought to identify HLA-A2 supertype-restricted epitopes from the LCMV proteome and evaluate them as vaccine determinants in HLA transgenic mice. We identified four HLA-A*0201-restricted peptides\u2014nucleoprotein NP<jats:sub>69-77<\/jats:sub>, glycoprotein precursor GPC<jats:sub>10-18<\/jats:sub>, GPC<jats:sub>447-455<\/jats:sub>, and zinc-binding protein Z<jats:sub>49-58<\/jats:sub>\u2014that displayed high-affinity binding (\u2264275 nM) to HLA-A*0201, induced CD8<jats:sup>+<\/jats:sup>T-cell responses of high functional avidity in HLA-A*0201 transgenic mice, and were naturally processed from native LCMV antigens in HLA-restricted human antigen presenting cells. One of the epitopes (GPC<jats:sub>447-455<\/jats:sub>), after peptide immunization of HLA-A*0201 mice, induced CD8<jats:sup>+<\/jats:sup>T cells capable of killing peptide-pulsed HLA-A*0201-restricted target cells in vivo and protected mice against lethal intracranial challenge with LCMV.<\/jats:p>","DOI":"10.1128\/jvi.02063-06","type":"journal-article","created":{"date-parts":[[2006,12,14]],"date-time":"2006-12-14T02:53:03Z","timestamp":1166064783000},"page":"2307-2317","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["HLA-A2-Restricted Protection against Lethal Lymphocytic Choriomeningitis"],"prefix":"10.1128","volume":"81","author":[{"given":"Jason","family":"Botten","sequence":"first","affiliation":[{"name":"Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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