F. Lozano Vigario , J. Molenaar , I. Simó Vesperinas , M. van der zon , N.S.A. Crone , M.J.M. de Jong , E. Hemme , M.A.C. Depuydt , L. Delfos , J. de Mol , M.N. Bernabé Kleijn , J.A.H.M. Peeters , A. Wezel , H.J. Smeets , R.T.N. Tjokrodirijo , A.H. de Ru , A. Kros , P.H.A. Quax , M.R. de Vries , J. Kuiper , B. Slütter
{"title":"人类动脉粥样硬化斑块的免疫肽组学分析确定动脉粥样硬化的抗原驱动因素","authors":"F. Lozano Vigario , J. Molenaar , I. Simó Vesperinas , M. van der zon , N.S.A. Crone , M.J.M. de Jong , E. Hemme , M.A.C. Depuydt , L. Delfos , J. de Mol , M.N. Bernabé Kleijn , J.A.H.M. Peeters , A. Wezel , H.J. Smeets , R.T.N. Tjokrodirijo , A.H. de Ru , A. Kros , P.H.A. Quax , M.R. de Vries , J. Kuiper , B. Slütter","doi":"10.1016/j.atherosclerosis.2025.120509","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aim</h3><div>Atherosclerosis has an auto-immune component driven by self-reactive T and B cells. Identifying their antigenic drivers may lead to new diagnosis and treatment approaches. Here, we aim to identify immunogenic T cell epitopes derived from atherosclerosis-relevant proteins such as ApoB100 by studying the repertoire of peptides presented by HLA in human plaques.</div></div><div><h3>Methods</h3><div>We used immunopeptidomics to identify peptides presented by HLA-DR molecules from plaques of patients that underwent endarterectomy surgery. We selected a set of 20 peptides derived from ApoB100 and studied the presence and cytokine profile of ApoB100-specific CD4<sup>+</sup> T cells in peripheral blood mononuclear cells (PBMCs) from atherosclerosis patients.</div></div><div><h3>Results</h3><div>revealed significant CD4<sup>+</sup> T cell activation in response to these ApoB100 peptides in 22–39 % of the patients, and this T cell response correlated positively with plaque vulnerability. These cells were characterized by production of both pro- and anti-inflammatory cytokines.</div></div><div><h3>Conclusion</h3><div>We show that immunopeptidomics can be a valid approach to new discover antigens in atherosclerosis.</div></div>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"409 ","pages":"Article 120509"},"PeriodicalIF":5.7000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis\",\"authors\":\"F. Lozano Vigario , J. Molenaar , I. Simó Vesperinas , M. van der zon , N.S.A. Crone , M.J.M. de Jong , E. Hemme , M.A.C. Depuydt , L. Delfos , J. de Mol , M.N. Bernabé Kleijn , J.A.H.M. Peeters , A. Wezel , H.J. Smeets , R.T.N. Tjokrodirijo , A.H. de Ru , A. Kros , P.H.A. Quax , M.R. de Vries , J. Kuiper , B. Slütter\",\"doi\":\"10.1016/j.atherosclerosis.2025.120509\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background and aim</h3><div>Atherosclerosis has an auto-immune component driven by self-reactive T and B cells. Identifying their antigenic drivers may lead to new diagnosis and treatment approaches. Here, we aim to identify immunogenic T cell epitopes derived from atherosclerosis-relevant proteins such as ApoB100 by studying the repertoire of peptides presented by HLA in human plaques.</div></div><div><h3>Methods</h3><div>We used immunopeptidomics to identify peptides presented by HLA-DR molecules from plaques of patients that underwent endarterectomy surgery. We selected a set of 20 peptides derived from ApoB100 and studied the presence and cytokine profile of ApoB100-specific CD4<sup>+</sup> T cells in peripheral blood mononuclear cells (PBMCs) from atherosclerosis patients.</div></div><div><h3>Results</h3><div>revealed significant CD4<sup>+</sup> T cell activation in response to these ApoB100 peptides in 22–39 % of the patients, and this T cell response correlated positively with plaque vulnerability. 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Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis
Background and aim
Atherosclerosis has an auto-immune component driven by self-reactive T and B cells. Identifying their antigenic drivers may lead to new diagnosis and treatment approaches. Here, we aim to identify immunogenic T cell epitopes derived from atherosclerosis-relevant proteins such as ApoB100 by studying the repertoire of peptides presented by HLA in human plaques.
Methods
We used immunopeptidomics to identify peptides presented by HLA-DR molecules from plaques of patients that underwent endarterectomy surgery. We selected a set of 20 peptides derived from ApoB100 and studied the presence and cytokine profile of ApoB100-specific CD4+ T cells in peripheral blood mononuclear cells (PBMCs) from atherosclerosis patients.
Results
revealed significant CD4+ T cell activation in response to these ApoB100 peptides in 22–39 % of the patients, and this T cell response correlated positively with plaque vulnerability. These cells were characterized by production of both pro- and anti-inflammatory cytokines.
Conclusion
We show that immunopeptidomics can be a valid approach to new discover antigens in atherosclerosis.
期刊介绍:
Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.