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. Hedrick; William W. Kwok; Alessandro Sette; Howard N. Hodis; Robert C. Kaplan; Klaus Ley

doi:10.1038/s44161-022-00063-3

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	462-475
Number of pages	14
Journal	Nature Cardiovascular Research
Volume	1
Issue number	5
DOIs	https://doi.org/10.1038/s44161-022-00063-3
State	Published - May 2022
Externally published	Yes

ASJC Scopus subject areas

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

Access to Document

10.1038/s44161-022-00063-3

Cite this

Saigusa, R., Roy, P., Freuchet, A., Gulati, R., Ghosheh, Y., Armstrong Suthahar, S. S., Durant, C. P., Hanna, D. B., Kiosses, W. B., Orecchioni, M., Wen, L., Wu, R., Kuniholm, M. H., Landay, A. L., Anastos, K., Tien, P. C., Gange, S. J., Kassaye, S., Vallejo, J., ... Ley, K. (2022). Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease. Nature Cardiovascular Research, 1(5), 462-475. https://doi.org/10.1038/s44161-022-00063-3

Saigusa, R, Roy, P, Freuchet, A, Gulati, R, Ghosheh, Y, Armstrong Suthahar, SS, Durant, CP, Hanna, DB, Kiosses, WB, Orecchioni, M, Wen, L, Wu, R, Kuniholm, MH, Landay, AL, Anastos, K, Tien, PC, Gange, SJ, Kassaye, S, Vallejo, J, Hedrick, CC, Kwok, WW, Sette, A, Hodis, HN, Kaplan, RC & Ley, K 2022, 'Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease', Nature Cardiovascular Research, vol. 1, no. 5, pp. 462-475. https://doi.org/10.1038/s44161-022-00063-3

@article{34700c90deb4488db400041bd9971775,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2022",

month = may,

doi = "10.1038/s44161-022-00063-3",

language = "English (US)",

volume = "1",

pages = "462--475",

journal = "Nature Cardiovascular Research",

issn = "2731-0590",

publisher = "Springer",

number = "5",

}

TY - JOUR

T1 - Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease

AU - Saigusa, Ryosuke

AU - Roy, Payel

AU - Freuchet, Antoine

AU - Gulati, Rishab

AU - Ghosheh, Yanal

AU - Armstrong Suthahar, Sujit Silas

AU - Durant, Christopher P.

AU - Hanna, David B.

AU - Kiosses, William B.

AU - Orecchioni, Marco

AU - Wen, Lai

AU - Wu, Runpei

AU - Kuniholm, Mark H.

AU - Landay, Alan L.

AU - Anastos, Kathryn

AU - Tien, Phyllis C.

AU - Gange, Stephen J.

AU - Kassaye, Seble

AU - Vallejo, Jenifer

AU - Hedrick, Catherine C.

AU - Kwok, William W.

AU - Sette, Alessandro

AU - Hodis, Howard N.

AU - Kaplan, Robert C.

AU - Ley, Klaus

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85137852350&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85137852350&partnerID=8YFLogxK

U2 - 10.1038/s44161-022-00063-3

DO - 10.1038/s44161-022-00063-3

M3 - Article

AN - SCOPUS:85137852350

SN - 2731-0590

VL - 1

SP - 462

EP - 475

JO - Nature Cardiovascular Research

JF - Nature Cardiovascular Research

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this