Atherosclerosis, Volume 409, 2 1 2025, Pages 120509 Immunopeptidomics analysis of human atherosclerosis plaques identifies antigenic drivers of atherosclerosis. Lozano Vigario F, Molenaar J, Simó Vesperinas I, van der Zon M, Crone NSA, de Jong MJM, Hemme E, Depuydt MAC, Delfos L, de Mol J, Bernabé Kleijn MN, Peeters JAHM, Wezel A, Smeets HJ, Tjokrodirijo RTN, de Ru AH, Kros A, Quax PHA, de Vries MR, Kuiper J, Bot I, van Veelen P, Slütter B
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.
