{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:55:19Z","timestamp":1791485719910,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014597","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014911","name":"Ministerstvo Obrany \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["DZRO-FVZ22-ZHN II"],"award-info":[{"award-number":["DZRO-FVZ22-ZHN II"]}],"id":[{"id":"10.13039\/501100014911","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001823","name":"Ministerstvo \u0160kolstv\u00ed, Ml\u00e1de\u017ee a T\u011blov\u00fdchovy","doi-asserted-by":"publisher","award":["SV\/FVZ202202"],"award-info":[{"award-number":["SV\/FVZ202202"]}],"id":[{"id":"10.13039\/501100001823","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019563","name":"Mikrobiologick\u00fd \u00dastav, Akademie V\u011bd \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["RVO 61388971"],"award-info":[{"award-number":["RVO 61388971"]}],"id":[{"id":"10.13039\/501100019563","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Grant Agency of the Czech Republic","award":["23-06605S"],"award-info":[{"award-number":["23-06605S"]}],"id":[{"id":"https:\/\/ror.org\/01pv73b02","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human tularemia is caused by infection with the intracellular bacterium\n                    <jats:italic>Francisella tularensis<\/jats:italic>\n                    . The ability of the bacterium to cause a severe pneumonic form of the disease has led to concerns in the field of biodefense and efforts to develop a vaccine.\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    LVS provides partial protection against fully virulent strains, with CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells playing a significant role in this protection, however the recognized bacterial antigens remain largely unknown. To identify these antigens, we screened MHC class II peptides presented by infected dendritic cells using mass spectrometry-based immunopeptidomics. We identified 57 MHC-II peptides from 23 different\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    LVS proteins. Most of these proteins were highly expressed in the bacterial proteome. Subsequent screening for IFN-\u03b3 responses identified ten peptides as immunogenic epitopes of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells following immunization of mice with\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    LVS, thereby revealing previously unknown specificity and breadth of the induced immune responses. Five epitopes, derived from the antigens FTL_1678, DacD, DnaK, FTL_1498, and MinD, represented the dominant epitopes that elicited a response in at least 80% of immunizations. Finally, a peptide vaccine containing these epitopes proved to be immunogenic in mice and contributed to the early control of bacterial replication following challenge with the virulent\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    FSC200 strain, although this alone was insufficient to ensure complete protection. Using immunopeptidomics, we have thus identified several immunogenic CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell epitopes and antigens of\n                    <jats:italic>F. tularensis<\/jats:italic>\n                    LVS. Beyond their potential role in the protective immune response, the identified epitopes may also enable the development of tools for characterizing antigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells in vaccination studies or T cell biology research.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014597","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:38:26Z","timestamp":1790703506000},"page":"e1014597","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunopeptidomics reveals conserved and abundant Francisella tularensis proteins as immunogenic CD4 T cell antigens in mice"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1253-4141","authenticated-orcid":true,"given":"Pavlina","family":"Laskova","sequence":"first","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5526-2065","authenticated-orcid":true,"given":"Stanislava","family":"Porkertova","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6950-5014","authenticated-orcid":true,"given":"Ondrej","family":"Ballek","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences","place":["Prague, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-1634","authenticated-orcid":true,"given":"Lucie","family":"Balonova","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4472-3343","authenticated-orcid":true,"given":"Jana","family":"Pavloskova","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-4316","authenticated-orcid":true,"given":"Ales","family":"Neuwirth","sequence":"additional","affiliation":[{"name":"Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences","place":["Prague, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Pavkova","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3027-1253","authenticated-orcid":true,"given":"Ivo","family":"Fabrik","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, University Hospital Hradec Kralove","place":["Hradec Kralove, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavol","family":"Lukac","sequence":"additional","affiliation":[{"name":"Laboratory of Immunotherapy, Institute of Microbiology of the Czech Academy of Sciences","place":["Prague, Czech Republic"]},{"name":"Charles University","place":["Prague, Czech Republic"],"department":["Department of Cell Biology, Faculty of Science"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Vannucci","sequence":"additional","affiliation":[{"name":"Laboratory of Immunotherapy, Institute of Microbiology of the Czech Academy of Sciences","place":["Prague, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik","family":"Filipp","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology, Institute of Molecular Genetics of the Czech Academy of Sciences","place":["Prague, Czech Republic"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Stulik","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4601-4523","authenticated-orcid":true,"given":"Marek","family":"Link","sequence":"additional","affiliation":[{"name":"University of Defence","place":["Hradec Kralove, Czech Republic"],"department":["Department of Molecular Pathology and Biology, Military Faculty of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ppat.1014597.ref001","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev-ento-011019-025134","article-title":"Ecology of Francisella tularensis","volume":"65","author":"3rd Telford SR","year":"2020","journal-title":"Annu Rev Entomol"},{"issue":"9","key":"ppat.1014597.ref002","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1016\/j.vaccine.2024.02.086","article-title":"Current vaccine strategies and novel approaches to combatting Francisella 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