Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis

Author(s):
Vigario, F.L.; Molenaar, J.; Vesperinas, I.S.; Zon, M. van der; Crone, N.S.A.; Jong, M.J.M. de; Hemme, E.; Depuydt, M.A.C.; Delfos, L.; Mol, J. de; Kleijn, M.N.B.; Peeters, J.A.H.M.; Wezel, A.; Smeets, H.J.; Tjokrodirijo, R.T.N.; Ru, A.H. de; Kros, A.; Quax, P.H.A.; Vries, M.R. de; Kuiper, J.; Bot, I.; Veelen, P. van; Slütter, B.
Published
2025
Publication type
Article / Letter to editor

Abstract

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.

ImmunopeptidomicsPBMCsAntigen-specific T cellsApoB100
Date issued
2025-09-06
Language
English
Publisher
ELSEVIER IRELAND LTD
Is part of
Atherosclerosis
hdl
1887/4298108
doi
10.1016/j.atherosclerosis.2025.120509