Neoself-antigens are the primary target for autoreactive T cells in human lupus.

Epstein-Bar virus HLA class II T cell recognition antigen presentation autoimmunity immune evasion invariant chain self tolerance

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
11 Sep 2024
Historique:
received: 17 10 2023
revised: 06 05 2024
accepted: 12 08 2024
medline: 15 9 2024
pubmed: 15 9 2024
entrez: 14 9 2024
Statut: aheadofprint

Résumé

Major histocompatibility complex class II (MHC-II) is the most significant genetic risk factor for systemic lupus erythematosus (SLE), but the nature of the self-antigens that trigger autoimmunity remains unclear. Unusual self-antigens, termed neoself-antigens, are presented on MHC-II in the absence of the invariant chain essential for peptide presentation. Here, we demonstrate that neoself-antigens are the primary target for autoreactive T cells clonally expanded in SLE. When neoself-antigen presentation was induced by deleting the invariant chain in adult mice, neoself-reactive T cells were clonally expanded, leading to the development of lupus-like disease. Furthermore, we found that neoself-reactive CD4

Identifiants

DOI: 10.1016/j.cell.2024.08.025 PMID: 39276775
pubmed: 39276775
pii: S0092-8674(24)00913-9
doi: 10.1016/j.cell.2024.08.025
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Shunsuke Mori (S)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.

Masako Kohyama (M)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Yoshiaki Yasumizu (Y)

Department of Experimental Immunology, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka 565-0871, Japan.

Asa Tada (A)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan.

Kaito Tanzawa (K)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Tatsuya Shishido (T)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Kazuki Kishida (K)

Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Hui Jin (H)

Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Masayuki Nishide (M)

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.

Shoji Kawada (S)

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.

Daisuke Motooka (D)

Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka 565-0871, Japan; Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

Daisuke Okuzaki (D)

Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka 565-0871, Japan; Single Cell Genomics, Human Immunology, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

Ryota Naito (R)

Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.

Wataru Nakai (W)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.

Teru Kanda (T)

Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.

Takayuki Murata (T)

Department of Virology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan; Department of Virology, Fujita Health University School of Medicine, Nagoya 470-1192, Japan.

Chikashi Terao (C)

Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 351-0198, Japan; Clinical Research Center, Shizuoka General Hospital, Shizuoka 420-8527, Japan; The Department of Applied Genetics, The School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.

Koichiro Ohmura (K)

Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan; Department of Rheumatology, Kobe City Medical Center General Hospital, Kobe, Hyogo 650-0047, Japan.

Noriko Arase (N)

Department of Dermatology, Graduate school of Medicine, Osaka University, Osaka 565-0871, Japan.

Tomohiro Kurosaki (T)

Laboratory of Lymphocyte Differentiation, WPI Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.

Manabu Fujimoto (M)

Department of Dermatology, Graduate school of Medicine, Osaka University, Osaka 565-0871, Japan.

Tadahiro Suenaga (T)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Department of Immunology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.

Atsushi Kumanogoh (A)

Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Center for advanced modalities and DDS, Osaka University, Osaka 565-0871, Japan.

Shimon Sakaguchi (S)

Department of Experimental Immunology, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Experimental Immunology, Institute for Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.

Yoshihiro Ogawa (Y)

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

Hisashi Arase (H)

Laboratory of Immunochemistry, World Premier International Immunology Frontier Research Centre, Osaka University, Osaka 565-0871, Japan; Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Center for advanced modalities and DDS, Osaka University, Osaka 565-0871, Japan; Center for Infectious Disease Education and Research, Osaka University, Osaka 565-0871, Japan. Electronic address: arase@biken.osaka-u.ac.jp.

Classifications MeSH