{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T08:11:45Z","timestamp":1793607105347,"version":"4.5.0"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"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":[[2006,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>TB10.4 is a newly identified antigen of<jats:italic>Mycobacterium tuberculosis<\/jats:italic>recognized by human and murine T cells upon mycobacterial infection. Here, we show that immunization with<jats:italic>Mycobacterium bovis<\/jats:italic>BCG induces a strong, genetically controlled, Th1 immune response against TB10.4 in mice. BALB\/c and C57BL\/6 strains behave as high and low responders to TB10.4 protein, respectively. The TB10.4:74-88 peptide was identified as an immunodominant CD4<jats:sup>+<\/jats:sup>T-cell epitope for<jats:italic>H-2<\/jats:italic><jats:sup><jats:italic>d<\/jats:italic><\/jats:sup>mice. Since recent results, as well as the present study, have raised interest in TB10.4 as a subunit vaccine, we analyzed immune responses induced by this antigen delivered by a new vector, the adenylate cyclase (CyaA) of<jats:italic>Bordetella pertussis<\/jats:italic>. CyaA is able to target dendritic cells and to deliver CD4<jats:sup>+<\/jats:sup>or CD8<jats:sup>+<\/jats:sup>T-cell epitopes to the major histocompatibility complex class II\/I molecule presentation pathways, triggering specific Th1 or cytotoxic T-lymphocyte (CTL) responses. Several CyaA harboring either the entire TB10.4 protein or various subfragments containing the TB10.4:20-28 CTL epitope were shown to induce TB10.4-specific Th1 CD4<jats:sup>+<\/jats:sup>and CD8<jats:sup>+<\/jats:sup>T-cell responses. However, none of the recombinant CyaA, injected in the absence of adjuvant, was able to induce protection against<jats:italic>M. tuberculosis<\/jats:italic>infection. In contrast, TB10.4 protein administered with a cocktail of strong adjuvants that triggered a strong Th1 CD4<jats:sup>+<\/jats:sup>T-cell response induced significant protection against<jats:italic>M. tuberculosis<\/jats:italic>challenge. These results confirm the potential value of the TB10.4 protein as a candidate vaccine and show that the presence of high frequencies of CD4<jats:sup>+<\/jats:sup>T cells specific to this strong immunogen correlates with protection against<jats:italic>M. tuberculosis<\/jats:italic>infection.<\/jats:p>","DOI":"10.1128\/iai.02086-05","type":"journal-article","created":{"date-parts":[[2006,5,19]],"date-time":"2006-05-19T23:52:41Z","timestamp":1148082761000},"page":"3396-3407","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["High Frequency of CD4<sup>+<\/sup>T Cells Specific for the TB10.4 Protein Correlates with Protection against<i>Mycobacterium tuberculosis<\/i>Infection"],"prefix":"10.1128","volume":"74","author":[{"given":"Sandra","family":"Hervas-Stubbs","sequence":"first","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Re\u0301gulations Immunitaires, Paris F-75015, France"},{"name":"INSERM, E 352, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh","family":"Majlessi","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Re\u0301gulations Immunitaires, Paris F-75015, France"},{"name":"INSERM, E 352, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Simsova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Morova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jesus","family":"Rojas","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Re\u0301gulations Immunitaires, Paris F-75015, France"},{"name":"INSERM, E 352, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cle\u0301mence","family":"Nouze\u0301","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Re\u0301gulations Immunitaires, Paris F-75015, France"},{"name":"INSERM, E 352, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscille","family":"Brodin","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Ge\u0301ne\u0301tique Mole\u0301culaire Bacte\u0301rienne, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sebo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Leclerc","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Unite\u0301 de Biologie des Re\u0301gulations Immunitaires, Paris F-75015, France"},{"name":"INSERM, E 352, Paris F-75015, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00519-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)01865-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.12.1973"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.791-795.2000"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.4049\/jimmunol.157.8.3527","volume":"157","year":"1996","unstructured":"Brandt, L., T. 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