The shared susceptibility epitope of HLA-DR4 binds citrullinated self-antigens and the TCR.


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
16 04 2021
Historique:
received: 30 07 2020
accepted: 18 03 2021
entrez: 17 4 2021
pubmed: 18 4 2021
medline: 1 3 2022
Statut: ppublish

Résumé

Individuals expressing HLA-DR4 bearing the shared susceptibility epitope (SE) have an increased risk of developing rheumatoid arthritis (RA). Posttranslational modification of self-proteins via citrullination leads to the formation of neoantigens that can be presented by HLA-DR4 SE allomorphs. However, in T cell-mediated autoimmunity, the interplay between the HLA molecule, posttranslationally modified epitope(s), and the responding T cell repertoire remains unclear. In HLA-DR4 transgenic mice, we show that immunization with a Fibβ-74cit

Identifiants

pubmed: 33863750
pii: 6/58/eabe0896
doi: 10.1126/sciimmunol.abe0896
pii:
doi:

Substances chimiques

Autoantigens 0
Epitopes, T-Lymphocyte 0
HLA-DR4 Antigen 0
HLA-DRB1 Chains 0
Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Auteurs

Jia Jia Lim (JJ)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Claerwen M Jones (CM)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Tiing Jen Loh (TJ)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Yi Tian Ting (YT)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Pirooz Zareie (P)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Khai L Loh (KL)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Nathan J Felix (NJ)

Janssen Research & Development LLC, Horsham, Philadelphia, PA, USA.

Anish Suri (A)

Janssen Research & Development, Turnhoutseweg 30, BE-2340, Beerse, Belgium.

Murray McKinnon (M)

Janssen Research & Development LLC, Horsham, Philadelphia, PA, USA.

Frederik Stevenaert (F)

Janssen Research & Development, Turnhoutseweg 30, BE-2340, Beerse, Belgium.

Ravi K Sharma (RK)

Rheumatology Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.

Lars Klareskog (L)

Rheumatology Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.

Vivianne Malmström (V)

Rheumatology Division, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 17177 Stockholm, Sweden.

Daniel G Baker (DG)

Janssen Research & Development LLC, Horsham, Philadelphia, PA, USA.

Anthony W Purcell (AW)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.

Hugh H Reid (HH)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. hugh.reid@monash.edu nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu.
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.

Nicole L La Gruta (NL)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. hugh.reid@monash.edu nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu.

Jamie Rossjohn (J)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia. hugh.reid@monash.edu nicole.la.gruta@monash.edu jamie.rossjohn@monash.edu.
Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, UK.

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Classifications MeSH