Human islet T cells are highly reactive to preproinsulin in type 1 diabetes
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- Amanda M. Anderson
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
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- Laurie G. Landry
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
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- Aimon A. Alkanani
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
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- Laura Pyle
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
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- Alvin C. Powers
- Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232;
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- Mark A. Atkinson
- Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610;
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- Clayton E. Mathews
- Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610;
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- Bart O. Roep
- Department of Diabetes Immunology, Diabetes and Metabolism Research Institute, Beckman Research Institute of City of Hope, Duarte, CA 91010;
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- Aaron W. Michels
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
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- Maki Nakayama
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO 80045;
抄録
<jats:title>Significance</jats:title> <jats:p>Insulin is a major self-antigen in type 1 diabetes (T1D), and as such, insulin-based immunotherapies have been trialed to treat the underlying autoimmunity but with minimal clinical benefit. Here, we comprehensively assessed reactivity to insulin and its precursor, preproinsulin, by CD8 T cells obtained from the pancreatic islets of organ donors with and without T1D. CD8 T cells highly reactive to peptides throughout the entire preproinsulin protein were only found in T1D donors at varying frequencies. Our results suggest considering the use of preproinsulin rather than just insulin for intervention immunotherapies and have important implications for identifying individuals that may respond to antigen-specific therapies designed to treat autoimmune disorders.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 118 (41), 2021-10-05
Proceedings of the National Academy of Sciences