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

16 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 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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s44161-022-00063-3

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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

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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.",

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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

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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.

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

Abstract

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