{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:11:35Z","timestamp":1788401495182,"version":"build-2803163510"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Dengue disease is a large public health problem that mainly afflicts tropical and subtropical regions. Understanding of the correlates of protection against dengue virus (DENV) is poor and hinders the development of a successful human vaccine. The present study aims to define DENV-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses in general and those of HLA alleles associated with dominant responses in particular. In human blood donors in Nicaragua, we observed a striking dominance of HLA B-restricted responses in general and of the allele B*35:01 in particular. Comparing these patterns to those in the general population of Sri Lanka, we found a strong correlation between restriction of the HLA allele and the breadth and magnitude of CD8\n            <jats:sup>+<\/jats:sup>\n            T cell responses, suggesting that HLA genes profoundly influence the nature of responses. The majority of gamma interferon (IFN-\u03b3) responses were associated with effector memory phenotypes, which were also detected in non-B*35:01-expressing T cells. However, only the B*35:01 DENV-specific T cells were associated with marked expression of the programmed death 1 protein (PD-1). These cells did not coexpress other inhibitory receptors and were able to proliferate in response to DENV-specific stimulation. Thus, the expression of particular HLA class I alleles is a defining characteristic influencing the magnitude and breadth of CD8 responses, and a distinct, highly differentiated phenotype is specifically associated with dominant CD8\n            <jats:sup>+<\/jats:sup>\n            T cells. These results are of relevance for both vaccine design and the identification of robust correlates of protection in natural immunity.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Dengue is an increasingly significant public health problem as its mosquito vectors spread over greater areas; no vaccines against the virus have yet been approved. An important step toward vaccine development is defining protective immune responses; toward that end, we here characterize the phenotype of the immunodominant T cell responses. These DENV-reactive T cells express high levels of the receptor programmed death 1 protein (PD-1), while those from disease-susceptible alleles do not. Not only does this represent a possible correlate of immunodominance, but it raises the hypothesis that PD-1 might be a regulator that prevents excessive damage while preserving antiviral function. Further, as this study employs distinct populations (Nicaraguan and Sri Lankan donors), we also confirmed that this pattern holds despite geographic and ethnic differences. This finding indicates that HLA type is the major determinant in shaping T cell responses.\n          <\/jats:p>","DOI":"10.1128\/jvi.02892-15","type":"journal-article","created":{"date-parts":[[2016,2,25]],"date-time":"2016-02-25T04:14:07Z","timestamp":1456373647000},"page":"4771-4779","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":74,"title":["Immunodominant Dengue Virus-Specific CD8\n            <sup>+<\/sup>\n            T Cell Responses Are Associated with a Memory PD-1\n            <sup>+<\/sup>\n            Phenotype"],"prefix":"10.1128","volume":"90","author":[{"given":"Ruklanthi","family":"de Alwis","sequence":"first","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Bangs","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Angelo","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristhiam","family":"Cerpas","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Virolog\u00eda, Centro Nacional de Diagn\u00f3stico y Referencia, Ministerio de Salud, Managua, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anira","family":"Fernando","sequence":"additional","affiliation":[{"name":"Genetech Research Institute, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sidney","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjoern","family":"Peters","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Gresh","sequence":"additional","affiliation":[{"name":"Sustainable Sciences Institute, Managua, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Balmaseda","sequence":"additional","affiliation":[{"name":"Laboratorio Nacional de Virolog\u00eda, Centro Nacional de Diagn\u00f3stico y Referencia, Ministerio de Salud, Managua, Nicaragua"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna D.","family":"de Silva","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"},{"name":"Genetech Research Institute, Colombo, Sri Lanka"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Sette","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Weiskopf","sequence":"additional","affiliation":[{"name":"Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060"},{"key":"e_1_3_2_3_2","first-page":"1","volume-title":"Dengue and dengue hemorrhagic fever","author":"Gubler DJ","year":"1997","unstructured":"Gubler DJ. 1997. Dengue and dengue hemorrhagic fever: its history and resurgence as a global public health problem, p 1\u201322. In Gubler DJ, Kuno G (ed), Dengue and dengue hemorrhagic fever. CAB International, New York, NY."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/140.4.527"},{"key":"e_1_3_2_5_2","first-page":"221","volume-title":"Dengue and dengue hemorrhagic fever","author":"Innis BL","year":"1997","unstructured":"Innis BL. 1997. Antibody responses to dengue virus infection, p 221\u2013243. In Gubler DJ, Kuno G (ed), Dengue and dengue hemorrhagic fever. CAB International, New York, NY."},{"key":"e_1_3_2_6_2","volume-title":"Dengue: guidelines for diagnosis, treatment, prevention and control: new edition","author":"WHO","year":"2009","unstructured":"WHO. 2009. Dengue: guidelines for diagnosis, treatment, prevention and control: new edition. WHO, Geneva, Switzerland."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1983.32.154"},{"key":"e_1_3_2_8_2","first-page":"653","article-title":"Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I","volume":"120","author":"Sangkawibha N","year":"1984","unstructured":"Sangkawibha N, Rojanasuphot S, Ahandrik S, Viriyapongse S, Jatanasen S, Salitul V, Phanthumachinda B, Halstead SB. 1984. Risk factors in dengue shock syndrome: a prospective epidemiologic study in Rayong, Thailand. I. The 1980 outbreak. Am J Epidemiol 120:653\u2013669.","journal-title":"The 1980 outbreak. Am J Epidemiol"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/315072"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3014"},{"key":"e_1_3_2_11_2","first-page":"25","article-title":"Circulating levels of tumour necrosis factor-alpha and interferon-gamma in patients with dengue and dengue haemorrhagic fever during an outbreak","volume":"123","author":"Chakravarti A","year":"2006","unstructured":"Chakravarti A, Kumaria R. 2006. Circulating levels of tumour necrosis factor-alpha and interferon-gamma in patients with dengue and dengue haemorrhagic fever during an outbreak. Indian J Med Res 123:25\u201330.","journal-title":"Indian J Med Res"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20080"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305227110"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv289"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3350"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803903"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2010_116"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04444"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.7.3532-3540.2006"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05115"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01177-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737857"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1590\/S0074-02761990000300012"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2000.63.5"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-0348-1_3"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050594"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02632-06"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-1"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013029"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2009.07.025"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0000304"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030852"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00455"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.9.1395"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801974"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401597"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00036-15"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2010.03.007"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142237"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02892-15","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02892-15","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:19:20Z","timestamp":1646489960000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02892-15"}},"subtitle":[],"editor":[{"given":"S.","family":"Perlman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1128\/JVI.02892-15"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02892-15","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5]]},"assertion":[{"value":"2015-11-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-20","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-04-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}