{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T05:19:21Z","timestamp":1741411161971,"version":"3.38.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB\/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9\/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9\/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9\/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.<\/jats:p>","DOI":"10.4049\/jimmunol.1401017","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T05:13:59Z","timestamp":1414473239000},"page":"5626-5636","source":"Crossref","is-referenced-by-count":7,"title":["Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations"],"prefix":"10.1093","volume":"193","author":[{"given":"Brenna J","family":"Hill","sequence":"first","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia A","family":"Darrah","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary","family":"Ende","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David R","family":"Ambrozak","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylie M","family":"Quinn","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sam","family":"Darko","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Gostick","sequence":"additional","affiliation":[{"name":"Institute of Infection and Immunity, Cardiff University School of Medicine , Cardiff CF14 4XN ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Wooldridge","sequence":"additional","affiliation":[{"name":"Faculty of Medical and Veterinary Sciences, University of Bristol , Bristol BS8 1TD ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo A","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Mathematics Institute, University of Warwick , Coventry CV4 7AL ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Venturi","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Centre for Vascular Research, University of New South Wales , Kensington 2052, New South Wales ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Larsen","sequence":"additional","affiliation":[{"name":"INSERM, U1135, Centre d\u2019Immunologie et des Maladies Infectieuses , F-75013 Paris ,","place":["France"]},{"name":"Centre d\u2019Immunologie et des Maladies Infectieuses, Sorbonne Universit\u00e9s, Universit\u00e9 Pierre et Marie Curie (Universit\u00e9 Paris 06) , CR7, F-75013 Paris ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miles P","family":"Davenport","sequence":"additional","affiliation":[{"name":"Computational Biology Group, Centre for Vascular Research, University of New South Wales , Kensington 2052, New South Wales ,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A","family":"Seder","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A","family":"Price","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 20892"},{"name":"Institute of Infection and Immunity, Cardiff University School of Medicine , Cardiff CF14 4XN ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel C","family":"Douek","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD 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