{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:03:33Z","timestamp":1790420613335,"version":"4.1.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"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":["Infect Immun"],"published-print":{"date-parts":[[2008,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The lethal toxin produced by\n            <jats:italic>Bacillus anthracis<\/jats:italic>\n            is a bipartite toxin in which the first protein, protective antigen (PA), transports the second protein, lethal factor, across the host cell membrane. We have previously shown that CD8\n            <jats:sup>+<\/jats:sup>\n            T-cell epitopes fused to a nontoxic derivative of lethal factor (LFn) are delivered into the host cell cytosol in a PA-dependent manner. Delivery of these antigens targets them to the intracellular major histocompatibility complex (MHC) class I processing and presentation pathway and leads to the stimulation of antigen-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in vivo. In this report, we describe the generation and characterization of LFn fusion proteins that include not only a CD8\n            <jats:sup>+<\/jats:sup>\n            T-cell epitope but also a CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell epitope. We first show that these fusion proteins induce antigen-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T-cell responses following incubation with dendritic cells in vitro or injection into mice. Stimulation of CD4\n            <jats:sup>+<\/jats:sup>\n            T cells by LFn fusion proteins does not require PA but is enhanced by PA in vitro. We also show that a single LFn fusion protein and PA can deliver antigen to both the MHC class II and the MHC class I pathways, resulting in the simultaneous induction of antigen-specific CD4\n            <jats:sup>+<\/jats:sup>\n            T cells and antigen-specific CD8\n            <jats:sup>+<\/jats:sup>\n            T cells in the same mouse. These results suggest that this toxin delivery system is capable of stimulating protective immune responses where effective immunization requires stimulation of both classes of T cells.\n          <\/jats:p>","DOI":"10.1128\/iai.01718-07","type":"journal-article","created":{"date-parts":[[2008,3,18]],"date-time":"2008-03-18T00:48:32Z","timestamp":1205801312000},"page":"2603-2611","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["Both CD4\n            <sup>+<\/sup>\n            and CD8\n            <sup>+<\/sup>\n            T Cells Respond to Antigens Fused to Anthrax Lethal Toxin"],"prefix":"10.1128","volume":"76","author":[{"given":"Christine A.","family":"Shaw","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Starnbach","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200211018"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53698-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.4.1723"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4696-4699.1998"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12531"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.2.615-619.1998"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.1998.00709.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1413"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2209"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00582.2004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/n35101999"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.062160399"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1465"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.7.3290-3296.1999"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.3037"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.22.12059"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.56.5.1066-1069.1988"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100301.064828"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.275"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90169-4"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80461-6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/87720"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001021"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1991.tb00796.x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.14.8027"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.03.022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1993.tb00936.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32036-7"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi015860m"},{"key":"e_1_3_2_31_2","first-page":"135","volume":"152","year":"2004","unstructured":"Mourez, M. 2004. 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