{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:10:03Z","timestamp":1793689803233,"version":"4.5.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Despite intensive lipid-lowering therapy, substantial residual cardiovascular risk persists, and antigen-specific adaptive immunity may contribute to the inflammatory burden that remains after lipid levels are controlled. Apolipoprotein B (ApoB)-containing lipoproteins accumulate in the arterial wall and undergo local modification. During this process, ApoB-containing material may be taken up by antigen-presenting cells, processed into self-peptides, and presented through MHC-II molecules to CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. This review focuses on ApoB antigen processing and presentation, the functional heterogeneity of ApoB-reactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, and emerging antigen-specific therapeutic approaches. Evidence from selected mouse models and human HLA-restricted systems indicates that ApoB-reactive T cells can acquire FoxP3\n                    <jats:sup>+<\/jats:sup>\n                    regulatory features. However, under hyperlipidemic conditions and during advanced disease, these regulatory features may overlap with, or be replaced by, T-bet\n                    <jats:sup>+<\/jats:sup>\n                    , memory-like, and pro-inflammatory phenotypes. Human studies using HLA-DR-p18 tetramers, activation-induced marker assays in peripheral blood mononuclear cells, and single-cell TCR analyses have begun to define disease-associated differences in ApoB-reactive T-cell states. Even so, current data do not yet prove longitudinal transitions within the same T-cell clones. Interpretation is further limited by HLA restriction, the rarity of ApoB-reactive cells, and relatively small study cohorts. In preclinical models, ApoB peptide vaccination and mucosal tolerance approaches suggest that antigen-specific immunity can be shifted toward regulation without broad immunosuppression. Taken together, ApoB-specific immunity appears to reflect a changing balance between tolerance and inflammation, influenced by antigen burden, HLA background, antigen-presenting cell status, and lesion stage.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1903006","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:17:26Z","timestamp":1789031846000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["ApoB-specific CD4+ T cells in atherosclerosis: MHC-II antigen presentation, T cell plasticity, and immune tolerance"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaobo","family":"Cao","sequence":"first","affiliation":[{"name":"Electrocardiography and Electroencephalography Room, Taizhou Second People\u2019s Hospital Affiliated to Yangzhou University","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongjing","family":"Mu","sequence":"additional","affiliation":[{"name":"The Affiliated Suzhou Hospital of Nanjing Medical University","place":["Suzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Taizhou Second People\u2019s Hospital Affiliated to Yangzhou University","place":["Taizhou, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1707914","article-title":"Antiinflammatory therapy with canakinumab for atherosclerotic disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw024","article-title":"Residual inflammatory risk: 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