A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

Autor:	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.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2019 May 30; Vol. 177 (6), pp. 1583-1599.e16.
DOI:	10.1016/j.cell.2019.05.007
Abstrakt:	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. (Copyright © 2019. Published by Elsevier Inc.)
Databáze:	MEDLINE
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