{"doi":"10.3389/fcvm.2022.1076808","title":"Single-cell transcriptomes and T cell receptors of vaccine-expanded apolipoprotein B-specific T cells","abstract":"Atherosclerotic cardiovascular diseases are the major cause of death worldwide. CD4 T cells responding to Apolipoprotein B (ApoB), the core protein of most lipoproteins, have been identified as critical disease modulators. In healthy individuals, ApoB-reactive (ApoB + ) CD4 T cells are mostly regulatory T cells (T regs ), which exert anti-inflammatory effects. Yet, they may obtain pro-inflammatory features and thus become proatherogenic. Evidence from animal studies suggests that vaccination against certain major histocompatibility complex (MHC) II-binding ApoB peptides induces an expansion of ApoB + T regs and thus confers atheroprotection. To date, in-depth phenotyping of vaccine-expanded ApoB + T cells has not yet been performed. To this end, we vaccinated C57BL/6J mice with the ApoB-peptide P6 (ApoB 978–993 TGAYSNASSTESASY) and performed single-cell RNA sequencing of tetramer-sorted P6 + T cells. P6 + cells were clonally expanded (one major, two minor clones) and formed a transcriptional cluster distinct from clusters mainly containing non-expanded P6 + and P6 – cells. Transcriptomic profiling revealed that most expanded P6 + cells had a strong T reg signature and highly expressed genes mediating suppressive functions. Yet, some expanded P6 + cells only had a residual T reg signature and expressed genes related to T helper 1 (T H 1) cells, which are proatherogenic. Modeling the T cell receptor (TCR) and P6:MHC-II interaction showed that only three amino acid residues in the α and β chain contact the P6 peptide in the MHC-II groove and thus determine the specificity of this TCR to P6. Our data begin to reveal the vaccination-induced response to an ApoB epitope.","journal":"Frontiers in Cardiovascular Medicine","year":2023,"id":370522,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":490441,"name":"Yanal Ghosheh","orcid":"0000-0002-3733-2098","position":1,"is_corresponding":false},{"id":324393,"name":"Holger Winkels","orcid":"0000-0003-1333-2031","position":2,"is_corresponding":false},{"id":490440,"name":"Kouji Kobiyama","orcid":"0000-0002-5846-4807","position":3,"is_corresponding":false},{"id":636274,"name":"Christopher P. Durant","orcid":"0000-0003-1374-8141","position":4,"is_corresponding":false},{"id":866044,"name":"Sujit Silas Armstrong Suthahar","orcid":"0000-0002-2538-4691","position":5,"is_corresponding":false},{"id":1039365,"name":"Simon Brunel","orcid":"0000-0001-7908-1840","position":6,"is_corresponding":false},{"id":490438,"name":"Payel Roy","orcid":"0000-0003-2511-068X","position":7,"is_corresponding":false},{"id":318062,"name":"Thamotharampillai Dileepan","orcid":"0000-0002-2810-6996","position":8,"is_corresponding":false},{"id":318063,"name":"Marc K. Jenkins","orcid":"0000-0001-8009-7655","position":9,"is_corresponding":false},{"id":1129937,"name":"Dirk M. Zajonc","orcid":"0000-0001-7215-1981","position":10,"is_corresponding":false},{"id":324398,"name":"Klaus Ley","orcid":"0000-0001-9339-3672","position":11,"is_corresponding":false},{"id":878440,"name":"Felix Sebastian Nettersheim","orcid":"0000-0002-4090-3357","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T01:15:41.237096Z","pmid":"36684560","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}