Single Cell Transcriptomics and TCR Reconstruction Reveal CD4 T Cell Response to MHC-II-restricted APOB Epitope in Human Cardiovascular Disease

Overview

Journal Nat Cardiovasc Res

Publisher Springer Nature

Specialty Cardiology & Vascular Diseases

Date 2022 Aug 22

PMID 35990517

Authors

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 Hedrick

William W Kwok

Alessandro Sette

Howard N Hodis

Robert C Kaplan

Klaus Ley

Affiliations

Soon will be listed here.

Abstract

Atherosclerosis is accompanied by a CD4 T cell response to apolipoprotein B (APOB). Major Histocompatibility Complex (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 cells from peripheral blood mononuclear cell samples from 8 DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD). Single cell RNA sequencing showed that transcriptomes of tetramer+ cells were between regulatory and memory T cells in healthy women and moved closer to memory T cells in women with sCVD. TCR sequencing of tetramer+ 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.

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