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CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates APCs as a damage\u2010associated molecular pattern to prime antigen\u2010specific na\u00efve T cells, which is crucial for T\u2010cell\u2010dependent anticardiolipin IgG antibody production in autoimmune diseases is unelucidated. Here, we show that CL increases the expression of costimulatory molecules in CD11c<jats:sup>+<\/jats:sup> APCs both in vitro and in vivo. CL activates CD11c<jats:sup>+<\/jats:sup> APCs via TLR2\u2010PI3K\u2010PKN1\u2010AKT\/p38MAPK\u2010NF\u2010\u03baB signaling. CD11c<jats:sup>+<\/jats:sup> APCs that have been activated by CL are sufficient to prime H\u2010Y peptide\u2010specific na\u00efve CD4<jats:sup>+<\/jats:sup> T cells and OVA\u2010specific na\u00efve CD8<jats:sup>+<\/jats:sup> T cells. TLR2 is necessary for anti\u2010CL IgG antibody responses in vivo. Intraperitoneal injection of CL does not activate CD11c<jats:italic><jats:sup>+<\/jats:sup><\/jats:italic> APCs in CD14 KO mice to the same extent as in wild\u2010type mice. CL binds to CD14 (Kd = 7 \u00d7 10<jats:sup>\u22127<\/jats:sup> M). CD14, but not MD2, plays a role in NF\u2010kB activation by CL, suggesting that CD14<jats:sup>+<\/jats:sup> macrophages contribute to recognizing CL. In summary, CL activates signaling pathways in CD11c<jats:sup>+<\/jats:sup> APCs through a mechanism similar to gram (+) bacteria and plays a crucial role in priming antigen\u2010specific na\u00efve T cells.<\/jats:p>","DOI":"10.1002\/eji.201747222","type":"journal-article","created":{"date-parts":[[2018,1,9]],"date-time":"2018-01-09T21:30:42Z","timestamp":1515533442000},"page":"777-790","source":"Crossref","is-referenced-by-count":18,"title":["Cardiolipin activates antigen\u2010presenting cells via TLR2\u2010PI3K\u2010PKN1\u2010AKT\/p38\u2010NF\u2010kB signaling to prime antigen\u2010specific na\u00efve T cells in mice"],"prefix":"10.1002","volume":"48","author":[{"given":"Jung\u2010Ah","family":"Cho","sequence":"first","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-9716","authenticated-orcid":false,"given":"Tae\u2010Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye\u2010Jung","family":"Moon","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye\u2010Kyung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-1029","authenticated-orcid":false,"given":"Seung\u2010Yong","family":"Seong","sequence":"additional","affiliation":[{"name":"Departments of Microbiology and Immunology Department of Biomedical Sciences, and Wide River Institute of Immunology Seoul National University College of Medicine  Jongno\u2010gu Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-688838"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.52.10.742"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141436"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09663"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e3181dcd28d"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6407"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2015.03.004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10992"},{"key":"e_1_2_7_10_1","first-page":"485","article-title":"Anti\u2010mitochondrial type 5 antibodies and anti\u2010cardiolipin antibodies in systemic lupus erythematosus and auto\u2010immune diseases","volume":"69","author":"Meyer O.","year":"1987","journal-title":"Clin. 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