biostudies-literatureDepuydt MACDutch Research Council (NWO)ZonMw112-125https://www.ebi.ac.uk/biostudies/studies/S-EPMC11041750biostudies-literatureUnknown2(2)Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4⁺ T cells, and these clonally expanded T cells expressed genes such as <i>CD69</i>, <i>FOS</i> and <i>FOSB</i>, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4⁺ T cells withNature cardiovascular researchSingle-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells.PMC11041750VI.Veni.212.1960912001191002595105013Hemme EPeeters JAHMde Mol JBot IBernabe Kleijn MNAFoks ACSlutter BDelfos LWezel Ade Borst GJde Winther MPJDepuydt MACSchaftenaar FHPrange KHMde Jong MJMPasterkamp GBoltjes AGoncalves LSmeets HJKuiper JfalseSingle-cell T cell receptor sequencing of paired human atherosclerotic plaques and blood reveals autoimmune-like features of expanded effector T cells.Atherosclerosis is a lipid-driven chronic inflammatory disease; however, whether it can be classified as an autoimmune disease remains unclear. In this study, we applied single-cell T cell receptor seqencing (scTCR-seq) on human carotid artery plaques and matched peripheral blood mononuclear cell samples to assess the extent of TCR clonality and antigen-specific activation within the various T cell subsets. We observed the highest degree of plaque-specific clonal expansion in effector CD4⁺ T cells, and these clonally expanded T cells expressed genes such as <i>CD69</i>, <i>FOS</i> and <i>FOSB</i>, indicative of recent TCR engagement, suggesting antigen-specific stimulation. CellChat analysis suggested multiple potential interactions of these effector CD4⁺ T cells with2023-01-01T00:00:00Z20232026-06-01T09:16:20.322Z2026-04-08T11:04:28.855ZS-EPMC110417503866590310.1038/s44161-022-00208-4