Dataset Information

Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis

ABSTRACT: 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. We used immunopeptidomics to identify peptides presented by HLA-DR molecules in 51 plaques from 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 22.4% of the patients, and this T cell response correlated positively with plaque vulnerability. Furthermore, the cytokine profile of these cells was characterized by production both pro- and anti-inflammatory cytokines.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Rayman Tjokrodirijo

LAB HEAD: Peter A. van Veelen

PROVIDER: PXD068446 | Pride | 2025-09-18

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	E20212000094a.raw	Raw
	E20212000094a2.raw	Raw
	E20212000094a3.raw	Raw
	P1189-3_Atherosclerotic_plaque_elutie_Class_II_plus_virus.msf	Msf

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Publications

Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis.

Lozano Vigario F F Molenaar J J Simó Vesperinas I I van der Zon M M Crone N S A NSA de Jong M J M MJM Hemme E E Depuydt M A C MAC Delfos L L de Mol J J Bernabé Kleijn M N MN Peeters J A H M JAHM Wezel A A Smeets H J HJ Tjokrodirijo R T N RTN de Ru A H AH Kros A A Quax P H A PHA de Vries M R MR Kuiper J J Bot I I van Veelen P P Slütter B B

Atherosclerosis 20250902

<h4>Background and aim</h4>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.<h4>Methods</h4>We used immunopeptidomics to identify peptides presented by HLA-DR molecules from plaques of pat ...[more]

PMID: 40916277

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Project description:Regression of atherosclerosis is an important clinical goal, however the pathways that mediate the resolution of atherosclerotic inflammation and reversal of plaques are poorly understood. Regulatory T cells (Tregs) have been shown to be atheroprotective, however numbers of these immunosuppressive cells decrease with disease progression. Using multiple independent mouse models of atherosclerosis regression, we demonstrate that an increase in plaque Tregs is a common signature of regressing plaques. To test if Tregs are required for the resolution of atherosclerotic inflammation and plaque regression during lipid-lowering therapy, we combined CD25 monoclonal antibody (PC61 mAb)-mediated Treg depletion with single-cell RNA-sequencing of immune cells in the plaque and conventional analyses of atherosclerosis. Single cell RNA-sequencing revealed that Tregs from aortic plaques shared some similarity with splenic Tregs, but were distinct from skin and colon Tregs supporting recent findings of tissue-dependent Treg heterogeneity. Furthermore, Tregs from progressing plaques expressed markers of natural Tregs derived from the thymus, whereas Tregs in regressing plaques lacked Nrp1 and Helios expression, suggesting that they are induced in the periphery during lipid lowering. Treatment of atherosclerotic mice with PC61 mAb effectively depleted Tregs in the blood and peripheral tissues, including plaques, and blocked the regression of atherosclerosis induced by apoB anti-sense oligonucleotides. Morphometric analyses revealed that control antibody-treated mice showed a 40% decrease in plaque burden and macrophage content under regression conditions, whereas PC61 mAb-treated mice showed no change in plaque size or inflammatory cell content compared to baseline. Moreover, Treg depletion enhanced inflammatory signaling and blocked tissue reparative functions of macrophages in the regressing plaque, including M2-polarization, efferocytosis and sensing of specialized pro-resolving lipid mediators. Together, these data establish essential roles for Tregs in the resolution of atherosclerotic inflammation and plaque remodeling during regression.