{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T18:29:18Z","timestamp":1773340158749,"version":"3.50.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2013,8,1]],"date-time":"2013-08-01T00:00:00Z","timestamp":1375315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Enterovirus 71 (EV71)\u2013associated hand-foot-mouth disease has become a major threat to public health in the Asia\u2013Pacific region. Although T cell immunity is closely correlated with clinical outcomes of EV71 infection, little is known about T cell immunity baseline against EV71 and T cell immunogenecity of EV71 Ags in the population, which has restricted our understanding of immunoprotection mechanisms. In this study, we investigated the cellular immune responses against the four structural Ags of EV71 and determined the immunohierarchy of these Ags in healthy adults. A low frequency of EV71-responsive T cells was detected circulating in peripheral blood, and broad T cell immune responses could be identified in most of the subjects after in vitro expansion. We demonstrated that the VP2 Ag with broad distribution of immunogenic peptides dominates T cell responses against EV71 compared with VP1, VP3, and VP4. Furthermore, the responses were illuminated to be mainly single IFN-\u03b3\u2013secreting CD4+ T cell dependent, indicating the previous natural acute viral infection of the adult population. Conservancy analysis of the immunogenic peptides revealed that moderately variant peptides were in the majority in coxsackievirus A16 (CV-A16) whereas most of the peptides were highly variant in polioviruses. Less efficient cross-reactivity against CV-A16 might broadly exist among individuals, whereas influences derived from poliovirus vaccination would be limited. Our findings suggest that the significance of VP2 Ag should be addressed in the future EV71-responsive immunological investigations. And the findings concerning the less efficient cross-reactivity against CV-A16 and limited influences from poliovirus vaccination in EV71-contacted population would contribute to a better understanding of immunoprotection mechanisms against enteroviruses.<\/jats:p>","DOI":"10.4049\/jimmunol.1301439","type":"journal-article","created":{"date-parts":[[2013,7,18]],"date-time":"2013-07-18T04:57:46Z","timestamp":1374123466000},"page":"1637-1647","source":"Crossref","is-referenced-by-count":24,"title":["VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population"],"prefix":"10.1093","volume":"191","author":[{"given":"Shuguang","family":"Tan","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Tan","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoman","family":"Sun","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangwen","family":"Lu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghua","family":"Yan","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Xu","sequence":"additional","affiliation":[{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George F","family":"Gao","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing 100049,","place":["China"]},{"name":"National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing 102206,","place":["China"]},{"name":"Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences , Beijing 100101,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,8,15]]},"reference":[{"key":"2025032405204233500_r1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000148922","article-title":"Epidemic of hand, foot and mouth disease associated with enterovirus 71 infection","volume":"9","author":"Hagiwara","year":"1978","journal-title":"Intervirology"},{"key":"2025032405204233500_r2","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJM199909233411301","article-title":"An epidemic of enterovirus 71 infection in Taiwan","volume":"341","author":"Ho","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"2025032405204233500_r3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1007\/BF01314873","article-title":"Virological diagnosis of enterovirus type 71 infections: experiences gained during an epidemic of acute CNS diseases in Hungary in 1978","volume":"71","author":"Nagy","year":"1982","journal-title":"Arch. Virol."},{"key":"2025032405204233500_r4","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/00006454-198807000-00007","article-title":"Outbreak of enterovirus 71 infection in Victoria, Australia, with a high incidence of neurologic involvement","volume":"7","author":"Gilbert","year":"1988","journal-title":"Pediatr. Infect. Dis. J."},{"key":"2025032405204233500_r5","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/00006454-198702000-00013","article-title":"Monoplegia caused by Enterovirus 71: an outbreak in Hong Kong","volume":"6","author":"Samuda","year":"1987","journal-title":"Pediatr. Infect. Dis. J."},{"key":"2025032405204233500_r6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1348-0421.2002.tb02743.x","article-title":"Outbreak of central nervous system disease associated with hand, foot, and mouth disease in Japan during the summer of 2000: detection and molecular epidemiology of enterovirus 71","volume":"46","author":"Fujimoto","year":"2002","journal-title":"Microbiol. Immunol."},{"key":"2025032405204233500_r7","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1128\/JCM.40.8.2823-2827.2002","article-title":"Direct detection of enterovirus 71 (EV71) in clinical specimens from a hand, foot, and mouth disease outbreak in Singapore by reverse transcription-PCR with universal enterovirus and EV71-specific primers","volume":"40","author":"Singh","year":"2002","journal-title":"J. Clin. 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