{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T02:47:14Z","timestamp":1767408434708},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virol J"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>All four dengue virus (DV) serotypes (D1V, D2V, D3V and D4V) can cause a series of disorders, ranging from mild dengue fever (DF) to severe dengue hemorrhagic fever and dengue shock syndrome (DHF\/DSS). Previous studies have revealed that DV serotype-specific CD8<jats:sup>+<\/jats:sup>T cells are involved in controlling DV infection. Serotype cross-reactive CD8<jats:sup>+<\/jats:sup>T-cells may contribute to the immunopathogenesis of DHF\/DSS. The aim of the study was to identify HLA-A*0201-binding peptides from four DV serotypes. We then examined their immunogenicity<jats:italic>in vivo<\/jats:italic>and cross-reactivity within heterologous peptides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>D1V-derived candidate CD8<jats:sup>+<\/jats:sup>T-cell epitopes were synthesized and evaluated for their affinity to the HLA-A*0201 molecule. Variant peptides representing heterologous D2V, D3V, D4V serotypes were synthesized. The immunogenicity of the high-affinity peptides were evaluated in HLA-A*0201 transgenic mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the seven D1V-derived candidate epitopes [D1V-NS4a<jats:sub>56\u201364<\/jats:sub>(MLLALIAVL), D1V-C<jats:sub>46\u201354<\/jats:sub>(LVMAFMAFL), D1V-NS4b<jats:sub>562\u2013570<\/jats:sub>(LLATSIFKL), D1V-NS2a<jats:sub>169\u2013177<\/jats:sub>(AMVLSIVSL), D1V-NS4a<jats:sub>140\u2013148<\/jats:sub>(GLLFMILTV), D1V-NS2a<jats:sub>144\u2013152<\/jats:sub>(QLWAALLSL) and D1V-NS4b<jats:sub>183\u2013191<\/jats:sub>(LLMRTTWAL)], three peptides [D1V-NS4a<jats:sub>140\u2013148<\/jats:sub>, D1V-NS2a<jats:sub>144\u2013152<\/jats:sub>and D1V-NS4b<jats:sub>183\u2013191<\/jats:sub>] had a high affinity for HLA-A*0201 molecules. Moreover, their variant peptides for D2V, D3V and D4V [D2V-NS4a<jats:sub>140\u2013148<\/jats:sub>(AILTVVAAT), D3V-NS4a<jats:sub>140-148<\/jats:sub>(GILTLAAIV), D4V-NS4a<jats:sub>140-148<\/jats:sub>(TILTIIGLI), D2V-NS2a<jats:sub>144\u2013152<\/jats:sub>(QLAVTIMAI), D3V-NS2a<jats:sub>144\u2013152<\/jats:sub>(QLWTALVSL), D4V-NS2a<jats:sub>143\u2013151<\/jats:sub>(QVGTLALSL), D2V-NS4b<jats:sub>182\u2013190<\/jats:sub>(LMMRTTWAL)<jats:sub>,<\/jats:sub>D3V-NS4b<jats:sub>182\u2013190<\/jats:sub>(LLMRTSWAL) and D4V-NS4b<jats:sub>179\u2013187<\/jats:sub>(LLMRTTWAF)] also had a high affinity for HLA-A*0201 molecules. Furthermore, CD8<jats:sup>+<\/jats:sup>T cells directed to these twelve peptides were induced in HLA-A*0201 transgenic mice following immunization with these peptides. Additionally, cross-reactivity within four peptides (D1V-NS4b<jats:sub>183\u2013191<\/jats:sub>, D2V-NS4b<jats:sub>182\u2013190,<\/jats:sub>D3V-NS4b<jats:sub>182\u2013190<\/jats:sub>and D4V-NS4b<jats:sub>179\u2013187<\/jats:sub>) was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Two novel serotype-specific HLA-A*0201-restricted CD8<jats:sup>+<\/jats:sup>T-cell epitopes (NS4a<jats:sub>140-148<\/jats:sub>and NS2a<jats:sub>144\u2013152<\/jats:sub>) and one cross-reactive HLA-A*0201-restricted CD8<jats:sup>+<\/jats:sup>T-cell epitopes which is similar to a previously identified epitope were identified in D1V-D4V. Combining prediction algorithms and HLA transgenic mice is an effective strategy to identify HLA-restricted epitopes. Serotype-specific epitopes would be used to determine the protective role of serotype-specific CD8<jats:sup>+<\/jats:sup>T cells, while cross-reactive epitopes may provide assistance in exploring the role of serotype cross-reactive CD8<jats:sup>+<\/jats:sup>T cells in the immunopathogenesis of DHF\/DSS.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1743-422x-9-259","type":"journal-article","created":{"date-parts":[[2012,11,5]],"date-time":"2012-11-05T07:14:13Z","timestamp":1352099653000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["HLA-A*0201-restricted CD8+T-cell epitopes identified in dengue viruses"],"prefix":"10.1186","volume":"9","author":[{"given":"Zhi-Liang","family":"Duan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke-Dong","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang-Long","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Quan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Sheng","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,11,5]]},"reference":[{"issue":"7","key":"1955_CR1","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/nrmicro1690","volume":"5","author":"SS Whitehead","year":"2007","unstructured":"Whitehead SS, Blaney JE, Durbin AP, Murphy BR: Prospects for a dengue virus vaccine. 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