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A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.
Ahmed, Rizwan; Omidian, Zahra; Giwa, Adebola; Cornwell, Benjamin; Majety, Neha; Bell, David R; Lee, Sangyun; Zhang, Hao; Michels, Aaron; Desiderio, Stephen; Sadegh-Nasseri, Scheherazade; Rabb, Hamid; Gritsch, Simon; Suva, Mario L; Cahan, Patrick; Zhou, Ruhong; Jie, Chunfa; Donner, Thomas; Hamad, Abdel Rahim A.
Afiliação
  • Ahmed R; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Omidian Z; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Giwa A; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Cornwell B; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Majety N; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Bell DR; Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
  • Lee S; Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA.
  • Zhang H; Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
  • Michels A; Barbara Davis Center for Diabetes, University of Colorado, Aurora, CO 80045, USA.
  • Desiderio S; Department of Molecular Biology and Genetics and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Sadegh-Nasseri S; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Rabb H; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Gritsch S; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
  • Suva ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Cahan P; Department of Molecular Biology and Genetics and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Zhou R; Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA; Department of Chemistry, Columbia University, New York, NY 10027, USA. Electronic address: rz24@columbia.edu.
  • Jie C; Department of Biochemistry and Nutrition, Des Moines University, Des Moines, IA 50312, USA.
  • Donner T; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Hamad ARA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ahamad@jhmi.edu.
Cell ; 177(6): 1583-1599.e16, 2019 05 30.
Article em En | MEDLINE | ID: mdl-31150624
ABSTRACT
T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. In concordance, a synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Moreover, mAbs bearing this clonotype are autoreactive against CD4 T cells and inhibit insulin tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute, and violators of this paradigm are likely key drivers of autoimmune diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Linfócitos T CD4-Positivos / Diabetes Mellitus Tipo 1 Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos B / Linfócitos T CD4-Positivos / Diabetes Mellitus Tipo 1 Idioma: En Ano de publicação: 2019 Tipo de documento: Article