Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Version history
  • Article usage
  • Citations to this article

Advertisement

CorrigendumAutoimmunity Free access | 10.1172/JCI35449C1

CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope

Ania Skowera, Richard J. Ellis, Ruben Varela-Calviño, Sefina Arif, Guo Cai Huang, Cassie Van-Krinks, Anna Zaremba, Chloe Rackham, Jennifer S. Allen, Timothy I.M. Tree, Min Zhao, Colin M. Dayan, Andrew K. Sewell, Wendy W. Unger, Jan W. Drijfhout, Ferry Ossendorp, Bart O. Roep, and Mark Peakman

Find articles by Skowera, A. in: JCI | PubMed | Google Scholar

Find articles by Ellis, R. in: JCI | PubMed | Google Scholar

Find articles by Varela-Calviño, R. in: JCI | PubMed | Google Scholar

Find articles by Arif, S. in: JCI | PubMed | Google Scholar

Find articles by Huang, G. in: JCI | PubMed | Google Scholar

Find articles by Van-Krinks, C. in: JCI | PubMed | Google Scholar

Find articles by Zaremba, A. in: JCI | PubMed | Google Scholar

Find articles by Rackham, C. in: JCI | PubMed | Google Scholar

Find articles by Allen, J. in: JCI | PubMed | Google Scholar

Find articles by Tree, T. in: JCI | PubMed | Google Scholar

Find articles by Zhao, M. in: JCI | PubMed | Google Scholar

Find articles by Dayan, C. in: JCI | PubMed | Google Scholar

Find articles by Sewell, A. in: JCI | PubMed | Google Scholar

Find articles by Unger, W. in: JCI | PubMed | Google Scholar

Find articles by Drijfhout, J. in: JCI | PubMed | Google Scholar

Find articles by Ossendorp, F. in: JCI | PubMed | Google Scholar

Find articles by Roep, B. in: JCI | PubMed | Google Scholar

Find articles by Peakman, M. in: JCI | PubMed | Google Scholar

Published September 1, 2009 - More info

Published in Volume 119, Issue 9 on September 1, 2009
J Clin Invest. 2009;119(9):2843–2843. https://doi.org/10.1172/JCI35449C1.
© 2009 The American Society for Clinical Investigation
Published September 1, 2009 - Version history
View PDF

Related article:

CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope
Ania Skowera, … , Bart O. Roep, Mark Peakman
Ania Skowera, … , Bart O. Roep, Mark Peakman
Research Article

CTLs are targeted to kill β cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope

  • Text
  • PDF
Abstract

The final pathway of β cell destruction leading to insulin deficiency, hyperglycemia, and clinical type 1 diabetes is unknown. Here we show that circulating CTLs can kill β cells via recognition of a glucose-regulated epitope. First, we identified 2 naturally processed epitopes from the human preproinsulin signal peptide by elution from HLA-A2 (specifically, the protein encoded by the A*0201 allele) molecules. Processing of these was unconventional, requiring neither the proteasome nor transporter associated with processing (TAP). However, both epitopes were major targets for circulating effector CD8+ T cells from HLA-A2+ patients with type 1 diabetes. Moreover, cloned preproinsulin signal peptide–specific CD8+ T cells killed human β cells in vitro. Critically, at high glucose concentration, β cell presentation of preproinsulin signal epitope increased, as did CTL killing. This study provides direct evidence that autoreactive CTLs are present in the circulation of patients with type 1 diabetes and that they can kill human β cells. These results also identify a mechanism of self-antigen presentation that is under pathophysiological regulation and could expose insulin-producing β cells to increasing cytotoxicity at the later stages of the development of clinical diabetes. Our findings suggest that autoreactive CTLs are important targets for immune-based interventions in type 1 diabetes and argue for early, aggressive insulin therapy to preserve remaining β cells.

Authors

Ania Skowera, Richard J. Ellis, Ruben Varela-Calviño, Sefina Arif, Guo Cai Huang, Cassie Van-Krinks, Anna Zaremba, Chloe Rackham, Jennifer S. Allen, Timothy I.M. Tree, Min Zhao, Colin M. Dayan, Andrew K. Sewell, Wendy Unger, Jan W. Drijfhout, Ferry Ossendorp, Bart O. Roep, Mark Peakman

×

Original citation: J. Clin. Invest.118:3390–3402 (2009). doi:10.1172/JCI35449.

Citation for this corrigendum: J. Clin. Invest.119:2843 (2009). doi:10.1172/JCI35449C1.

During the preparation of the manuscript, Wendy W. Unger’s name was inadvertently presented incorrectly in the author list. The correct author list appears above.

The authors regret the error.

Version history
  • Version 1 (September 1, 2009): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts