{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T05:44:41Z","timestamp":1761630281314},"reference-count":47,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2001,8,15]],"date-time":"2001-08-15T00:00:00Z","timestamp":997833600000},"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":[[2001,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Subdominant CD8<jats:sup>+<\/jats:sup>T-cell responses contribute to control of several viral infections and to vaccine-induced immunity. Here, using the lymphocytic choriomeningitis virus model, we demonstrate that subdominant epitopes can be more reliably identified by DNA immunization than by other methods, permitting the identification, in the virus nucleoprotein, of two overlapping subdominant epitopes: one presented by L<jats:sup>d<\/jats:sup>and the other presented by K<jats:sup>d<\/jats:sup>. This subdominant sequence confers immunity as effective as that induced by the dominant epitope, against which &gt;90% of the antiviral CD8<jats:sup>+<\/jats:sup>T cells are normally directed. We compare the kinetics of the dominant and subdominant responses after vaccination with those following subsequent viral infection. The dominant CD8<jats:sup>+<\/jats:sup>response expands more rapidly than the subdominant responses, but after virus infection is cleared, mice which had been immunized with the \u201cdominant\u201d vaccine have a pool of memory T cells focused almost entirely upon the dominant epitope. In contrast, after virus infection, mice which had been immunized with the \u201csubdominant\u201d vaccine retain both dominant and subdominant memory cells. During the acute phase of the immune response, the acquisition of cytokine responsiveness by subdominant CD8<jats:sup>+<\/jats:sup>T cells precedes their development of lytic activity. Furthermore, in both dominant and subdominant populations, lytic activity declines more rapidly than cytokine responsiveness. Thus, the lysis<jats:sup>low<\/jats:sup>-cytokine<jats:sup>competent<\/jats:sup>phenotype associated with most memory CD8<jats:sup>+<\/jats:sup>T cells appears to develop soon after antigen clearance. Finally, lytic activity differs among CD8<jats:sup>+<\/jats:sup>T-cell populations with different epitope specificities, suggesting that vaccines can be designed to selectively induce CD8<jats:sup>+<\/jats:sup>T cells with distinct functional attributes.<\/jats:p>","DOI":"10.1128\/jvi.75.16.7399-7409.2001","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:37Z","timestamp":1027764397000},"page":"7399-7409","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Two Overlapping Subdominant Epitopes Identified by DNA Immunization Induce Protective CD8<sup>+<\/sup>T-Cell Populations with Differing Cytolytic Activities"],"prefix":"10.1128","volume":"75","author":[{"given":"Fernando","family":"Rodriguez","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California,1 and"},{"name":"<!--label omitted: 2-->Servicio de Hematologia, Hospital Universitario 12 de Octubre, Madrid, Spain2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark K.","family":"Slifka","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Harkins","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Lindsay","family":"Whitton","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California,1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00546-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<291::AID-IMMU291>3.0.CO;2-K"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1725"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-205"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.4049\/jimmunol.160.5.2425","article-title":"Induction of CD8+ T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination","volume":"160","author":"Chen Y.","year":"1998","unstructured":"Chen Y. Webster R. G. Woodland D. L. Induction of CD8+ T cell responses to dominant and subdominant epitopes and protective immunity to Sendai virus infection by DNA vaccination.J. Immunol. 160 1998 2425 2432","journal-title":"J. Immunol."},{"key":"e_1_3_2_7_2","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.4049\/jimmunol.148.10.3004","article-title":"Role of endogenous peptides in murine allogenic cytotoxic T cell responses assessed using transfectants of the antigen-processing mutant 174xCEM.T2","volume":"148","author":"Crumpacker D. B.","year":"1992","unstructured":"Crumpacker D. B. Alexander J. Cresswell P. Engelhard V. H. Role of endogenous peptides in murine allogenic cytotoxic T cell responses assessed using transfectants of the antigen-processing mutant 174xCEM.T2.J. Immunol. 148 1992 3004 3011","journal-title":"J. Immunol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.4.2715-2721.1997"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.187.10.1647-b"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65585-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-212"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(96)80034-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80295-2"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8286-8291.2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/10.10.1441"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.5.1653-1658.1988"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/369031a0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.10.4311-4316.1989"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.9.2482"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.2.1261-1264.1995"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.186.6.859"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(96)10011-6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.4292"},{"key":"e_1_3_2_24_2","first-page":"97","article-title":"Prospects for T cell immunotherapy of tumours by vaccination with immunodominant and subdominant peptides","volume":"187","author":"Melief C. J.","year":"1994","unstructured":"Melief C. J. Kast W. M. Prospects for T cell immunotherapy of tumours by vaccination with immunodominant and subdominant peptides.Ciba Found. Symp. 187 1994 97 104","journal-title":"Ciba Found. Symp."},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9148"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/346629a0"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(93)90277-R"},{"key":"e_1_3_2_28_2","doi-asserted-by":"crossref","first-page":"4266","DOI":"10.4049\/jimmunol.156.11.4266","article-title":"Studies of tum: peptide analogs define an alternative anchor that can be utilized by Ld ligands lacking the consensus P2 anchor","volume":"156","author":"Robinson R. A.","year":"1996","unstructured":"Robinson R. A. Lee D. R. Studies of tum: peptide analogs define an alternative anchor that can be utilized by Ld ligands lacking the consensus P2 anchor.J. Immunol. 156 1996 4266 4273","journal-title":"J. Immunol."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.5174-5181.1998"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8497-8503.1997"},{"key":"e_1_3_2_31_2","doi-asserted-by":"crossref","first-page":"5366","DOI":"10.4049\/jimmunol.158.11.5366","article-title":"Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection","volume":"158","author":"Selin L. K.","year":"1997","unstructured":"Selin L. K. Welsh R. M. Cytolytically active memory CTL present in lymphocytic choriomeningitis virus-immune mice after clearance of virus infection.J. Immunol. 158 1997 5366 5373","journal-title":"J. Immunol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/43454"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V90.5.2103"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.1.208"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90159-0"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8456302"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.7.5110-5114.1997"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8934"},{"key":"e_1_3_2_39_2","doi-asserted-by":"crossref","first-page":"5543","DOI":"10.4049\/jimmunol.157.12.5543","article-title":"Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection","volume":"157","author":"van der Most R. G.","year":"1996","unstructured":"van der Most R. G. Sette A. Oseroff C. Alexander J. Murali-Krishna K. Lau L. L. Southwood S. Sidney J. Chesnut R. W. Matloubian M. Ahmed R. Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection.J. Immunol. 157 1996 5543 5554","journal-title":"J. Immunol."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.23.10854"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.11.7147-7151.1995"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.1.348-352.1993"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.10.4303-4310.1989"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090097697"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.4.2684-2688.1995"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.1996.tb00290.x"},{"key":"e_1_3_2_47_2","doi-asserted-by":"crossref","first-page":"4010","DOI":"10.4049\/jimmunol.154.8.4010","article-title":"Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein","volume":"154","author":"Zarozinski C. C.","year":"1995","unstructured":"Zarozinski C. C. Fynan E. F. Selin L. K. Robinson H. L. Welsh R. M. Protective CTL-dependent immunity and enhanced immunopathology in mice immunized by particle bombardment with DNA encoding an internal virion protein.J. Immunol. 154 1995 4010 4017","journal-title":"J. Immunol."},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830240822"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.75.16.7399-7409.2001","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.75.16.7399-7409.2001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T15:53:36Z","timestamp":1682265216000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.75.16.7399-7409.2001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,8,15]]},"references-count":47,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2001,8,15]]}},"alternative-id":["10.1128\/JVI.75.16.7399-7409.2001"],"URL":"https:\/\/doi.org\/10.1128\/jvi.75.16.7399-7409.2001","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,8,15]]},"assertion":[{"value":"2001-02-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-08-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}