Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease

Ryosuke Saigusa, Payel Roy, Antoine Freuchet, Rishab Gulati, Yanal Ghosheh, Sujit Silas Armstrong Suthahar, Christopher P. Durant, David B. Hanna, William B. Kiosses, Marco Orecchioni, Lai Wen, Runpei Wu, Mark H. Kuniholm, Alan L. Landay, Kathryn Anastos, Phyllis C. Tien, Stephen J. Gange, Seble Kassaye, Jenifer Vallejo, Catherine C. HedrickWilliam W. Kwok, Alessandro Sette, Howard N. Hodis, Robert C. Kaplan, Klaus Ley

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Atherosclerosis is accompanied by a CD4 T cell response to apolipoprotein B (APOB). Major histocompatibility complex class II (MHC-II) tetramers can be used to isolate antigen-specific CD4 T cells by flow sorting. Here, we produce, validate and use an MHC-II tetramer, DRB1*07:01 APOB-p18, to sort APOB-p18-specific CD4 T cells from peripheral blood mononuclear cell samples from eight DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD). Single-cell RNA sequencing showed that transcriptomes of tetramer-positive cells were between regulatory and memory T cells in healthy women and moved closer to memory T cells in women with sCVD. T cell receptor sequencing of tetramer-positive cells showed clonal expansion and V and J segment usage similar to those found in regulatory T cells. These findings suggest that APOB-specific regulatory T cells may switch to a more memory-like phenotype in women with atherosclerosis. Mouse studies showed that such switched cells promote atherosclerosis.

Original languageEnglish (US)
Pages (from-to)462-475
Number of pages14
JournalNature Cardiovascular Research
Volume1
Issue number5
DOIs
StatePublished - May 2022
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Cell Biology
  • Medicine (miscellaneous)
  • Cardiology and Cardiovascular Medicine

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