Journal article
Autoantigen-Induced Focusing of Vβ13+ T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
Diabetes (New York, N.Y.), v 63(2), pp 596-604
Feb 2014
PMID: 24150607
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor (TCR)-variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ13
+
T cells with an allele-specific monoclonal antibody prevents disease in multiple rat strains. To investigate the role of Vβ13 early in diabetes, we examined islet T-cell transcripts in susceptible (LEW.1WR1) and resistant (LEW.1W and Wistar Furth) strains induced with polyinosinic:polycytidylic acid. Vβ13
+
T cells displayed antigenic focusing in LEW.1WR1 islets 5 days postinduction and were characterized by a substantial decrease in complementarity determining region 3 diversity. This occurred prior to significant islet T-cell accumulation (day 7) or frank diabetes (days 10–14). Vβ13
+
transcripts increased in LEW.1WR1 islets during diabetes progression, but not in resistant rats. We also analyzed transcript clonality of rat TCR-Vα5, an ortholog of the dominant TCR-Vα chain found on insulin B:9-23–reactive T cells in nonobese diabetic rat islets. We observed clonal expansion of Vα5
+
transcripts in prediabetic LEW.1WR1 islets, suggesting that rat Vα5 is also an important component of islet autoantigen recognition. These data provide additional evidence that genome-encoded TCR sequences are important determinants of genetic susceptibility to T1D.
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Details
- Title
- Autoantigen-Induced Focusing of Vβ13+ T Cells Precedes Onset of Autoimmune Diabetes in the LEW.1WR1 Rat
- Creators
- Ryan A Eberwine - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PALaura Cort - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PAMichael Habib - Division of Endocrinology & Metabolism, Department of Medicine, University of Massachusetts Medical School, Worcester, MAJohn P Mordes - Division of Endocrinology & Metabolism, Department of Medicine, University of Massachusetts Medical School, Worcester, MAElizabeth P Blankenhorn - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA
- Publication Details
- Diabetes (New York, N.Y.), v 63(2), pp 596-604
- Publisher
- American Diabetes Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology; [Retired Faculty]
- Web of Science ID
- WOS:000331110000027
- Scopus ID
- 2-s2.0-84893050777
- Other Identifier
- 991014877794104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Endocrinology & Metabolism