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HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

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HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. / Wang, Jian; Jelcic, Ivan; Mühlenbruch, Lena; Haunerdinger, Veronika; Toussaint, Nora C; Zhao, Yingdong; Cruciani, Carolina; Faigle, Wolfgang; Naghavian, Reza; Foege, Magdalena; Binder, Thomas M C; Eiermann, Thomas; Opitz, Lennart; Fuentes-Font, Laura; Reynolds, Richard; Kwok, William W; Nguyen, Julie T; Lee, Jar-How; Lutterotti, Andreas; Münz, Christian; Rammensee, Hans-Georg; Hauri-Hohl, Mathias; Sospedra, Mireia; Stevanovic, Stefan; Martin, Roland.

In: CELL, Vol. 183, No. 5, 25.11.2020, p. 1264-1281.e20.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Wang, J, Jelcic, I, Mühlenbruch, L, Haunerdinger, V, Toussaint, NC, Zhao, Y, Cruciani, C, Faigle, W, Naghavian, R, Foege, M, Binder, TMC, Eiermann, T, Opitz, L, Fuentes-Font, L, Reynolds, R, Kwok, WW, Nguyen, JT, Lee, J-H, Lutterotti, A, Münz, C, Rammensee, H-G, Hauri-Hohl, M, Sospedra, M, Stevanovic, S & Martin, R 2020, 'HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis', CELL, vol. 183, no. 5, pp. 1264-1281.e20. https://doi.org/10.1016/j.cell.2020.09.054

APA

Wang, J., Jelcic, I., Mühlenbruch, L., Haunerdinger, V., Toussaint, N. C., Zhao, Y., Cruciani, C., Faigle, W., Naghavian, R., Foege, M., Binder, T. M. C., Eiermann, T., Opitz, L., Fuentes-Font, L., Reynolds, R., Kwok, W. W., Nguyen, J. T., Lee, J-H., Lutterotti, A., ... Martin, R. (2020). HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. CELL, 183(5), 1264-1281.e20. https://doi.org/10.1016/j.cell.2020.09.054

Vancouver

Wang J, Jelcic I, Mühlenbruch L, Haunerdinger V, Toussaint NC, Zhao Y et al. HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. CELL. 2020 Nov 25;183(5):1264-1281.e20. https://doi.org/10.1016/j.cell.2020.09.054

Bibtex

@article{a3f63395bdde49c28543e76cdc376c8e,
title = "HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis",
abstract = "The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4+ T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4+ T cells in MS.",
keywords = "Adult, Aged, Alleles, Antigens/immunology, B-Lymphocytes/immunology, CD4-Positive T-Lymphocytes/immunology, Cells, Cultured, Cross Reactions/immunology, Female, HLA-DR Serological Subtypes/immunology, Humans, Immunologic Memory, Male, Middle Aged, Monocytes/immunology, Multiple Sclerosis/immunology, Peptides/immunology, Proteome/metabolism, T-Lymphocytes/immunology, Young Adult",
author = "Jian Wang and Ivan Jelcic and Lena M{\"u}hlenbruch and Veronika Haunerdinger and Toussaint, {Nora C} and Yingdong Zhao and Carolina Cruciani and Wolfgang Faigle and Reza Naghavian and Magdalena Foege and Binder, {Thomas M C} and Thomas Eiermann and Lennart Opitz and Laura Fuentes-Font and Richard Reynolds and Kwok, {William W} and Nguyen, {Julie T} and Jar-How Lee and Andreas Lutterotti and Christian M{\"u}nz and Hans-Georg Rammensee and Mathias Hauri-Hohl and Mireia Sospedra and Stefan Stevanovic and Roland Martin",
note = "Copyright {\textcopyright} 2020 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2020",
month = nov,
day = "25",
doi = "10.1016/j.cell.2020.09.054",
language = "English",
volume = "183",
pages = "1264--1281.e20",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

RIS

TY - JOUR

T1 - HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis

AU - Wang, Jian

AU - Jelcic, Ivan

AU - Mühlenbruch, Lena

AU - Haunerdinger, Veronika

AU - Toussaint, Nora C

AU - Zhao, Yingdong

AU - Cruciani, Carolina

AU - Faigle, Wolfgang

AU - Naghavian, Reza

AU - Foege, Magdalena

AU - Binder, Thomas M C

AU - Eiermann, Thomas

AU - Opitz, Lennart

AU - Fuentes-Font, Laura

AU - Reynolds, Richard

AU - Kwok, William W

AU - Nguyen, Julie T

AU - Lee, Jar-How

AU - Lutterotti, Andreas

AU - Münz, Christian

AU - Rammensee, Hans-Georg

AU - Hauri-Hohl, Mathias

AU - Sospedra, Mireia

AU - Stevanovic, Stefan

AU - Martin, Roland

N1 - Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2020/11/25

Y1 - 2020/11/25

N2 - The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4+ T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4+ T cells in MS.

AB - The HLA-DR15 haplotype is the strongest genetic risk factor for multiple sclerosis (MS), but our understanding of how it contributes to MS is limited. Because autoreactive CD4+ T cells and B cells as antigen-presenting cells are involved in MS pathogenesis, we characterized the immunopeptidomes of the two HLA-DR15 allomorphs DR2a and DR2b of human primary B cells and monocytes, thymus, and MS brain tissue. Self-peptides from HLA-DR molecules, particularly from DR2a and DR2b themselves, are abundant on B cells and thymic antigen-presenting cells. Furthermore, we identified autoreactive CD4+ T cell clones that can cross-react with HLA-DR-derived self-peptides (HLA-DR-SPs), peptides from MS-associated foreign agents (Epstein-Barr virus and Akkermansia muciniphila), and autoantigens presented by DR2a and DR2b. Thus, both HLA-DR15 allomorphs jointly shape an autoreactive T cell repertoire by serving as antigen-presenting structures and epitope sources and by presenting the same foreign peptides and autoantigens to autoreactive CD4+ T cells in MS.

KW - Adult

KW - Aged

KW - Alleles

KW - Antigens/immunology

KW - B-Lymphocytes/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - Cells, Cultured

KW - Cross Reactions/immunology

KW - Female

KW - HLA-DR Serological Subtypes/immunology

KW - Humans

KW - Immunologic Memory

KW - Male

KW - Middle Aged

KW - Monocytes/immunology

KW - Multiple Sclerosis/immunology

KW - Peptides/immunology

KW - Proteome/metabolism

KW - T-Lymphocytes/immunology

KW - Young Adult

U2 - 10.1016/j.cell.2020.09.054

DO - 10.1016/j.cell.2020.09.054

M3 - SCORING: Journal article

C2 - 33091337

VL - 183

SP - 1264-1281.e20

JO - CELL

JF - CELL

SN - 0092-8674

IS - 5

ER -