دورية أكاديمية
An Insulin-Chromogranin A Hybrid Peptide Activates DR11-Restricted T Cells in Human Type 1 Diabetes.
| العنوان: | An Insulin-Chromogranin A Hybrid Peptide Activates DR11-Restricted T Cells in Human Type 1 Diabetes. |
|---|---|
| المؤلفون: | Callebaut A; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA.; Laboratory of Clinical and Experimental Endocrinology, Catholic University of Leuven, Leuven, Belgium., Guyer P; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA., Baker RL; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO., Gallegos JB; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO.; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO., Hohenstein AC; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO., Gottlieb PA; Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO., Mathieu C; Laboratory of Clinical and Experimental Endocrinology, Catholic University of Leuven, Leuven, Belgium., Overbergh L; Laboratory of Clinical and Experimental Endocrinology, Catholic University of Leuven, Leuven, Belgium., Haskins K; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO., James EA; Center for Translational Immunology, Benaroya Research Institute, Seattle, WA. |
| المصدر: | Diabetes [Diabetes] 2024 May 01; Vol. 73 (5), pp. 743-750. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Insulin* , Diabetes Mellitus, Type 1*, Humans ; Animals ; Mice ; T-Lymphocytes ; Proinsulin ; C-Peptide ; Chromogranin A ; Peptides ; Insulin, Regular, Human ; Epitopes ; Peptide Fragments |
| مستخلص: | Hybrid insulin peptides (HIPs) formed through covalent cross-linking of proinsulin fragments to secretory granule peptides are detectable within murine and human islets. The 2.5HIP (C-peptide-chromogranin A [CgA] HIP), recognized by the diabetogenic BDC-2.5 clone, is a major autoantigen in the nonobese diabetic mouse. However, the relevance of this epitope in human disease is currently unclear. A recent study probed T-cell reactivity toward HIPs in patients with type 1 diabetes, documenting responses in one-third of the patients and isolating several HIP-reactive T-cell clones. In this study, we isolated a novel T-cell clone and showed that it responds vigorously to the human equivalent of the 2.5HIP (designated HIP9). Although the responding patient carried the risk-associated DRB1*04:01/DQ8 haplotype, the response was restricted by DRB1*11:03 (DR11). HLA class II tetramer staining revealed higher frequencies of HIP9-reactive T cells in individuals with diabetes than in control participants. Furthermore, in DR11+ participants carrying the DRB4 allele, HIP9-reactive T-cell frequencies were higher than observed frequencies for the immunodominant proinsulin 9-28 epitope. Finally, there was a negative correlation between HIP9-reactive T-cell frequency and age at diagnosis. These results provide direct evidence that this C-peptide-CgA HIP is relevant in human type 1 diabetes and suggest a mechanism by which nonrisk HLA haplotypes may contribute to the development of β-cell autoimmunity. (© 2024 by the American Diabetes Association.) |
| References: | J Autoimmun. 2017 Mar;78:11-18. (PMID: 27802879) Semin Immunol. 2023 Mar;66:101730. (PMID: 36827760) J Clin Invest. 1999 Dec;104(12):R63-7. (PMID: 10606632) Diabetologia. 2021 Jan;64(1):15-25. (PMID: 33084970) J Proteome Res. 2019 Mar 1;18(3):814-825. (PMID: 30585061) Diabetes Care. 2000 Oct;23(10):1516-26. (PMID: 11023146) Diabetes Care. 2008 Jul;31(7):1392-6. (PMID: 18356404) World J Diabetes. 2015 Apr 15;6(3):380-90. (PMID: 25897349) Clin Exp Immunol. 2016 Jan;183(1):8-15. (PMID: 26313217) J Immunol. 2016 Jan 1;196(1):39-43. (PMID: 26608914) Diabetes. 2020 Jul;69(7):1492-1502. (PMID: 32291282) J Immunol. 2018 Dec 15;201(12):3524-3533. (PMID: 30455401) Nat Med. 2016 Dec;22(12):1482-1487. (PMID: 27798614) Diabetes. 2018 Sep;67(9):1836-1846. (PMID: 29976617) Nat Immunol. 2020 Apr;21(4):455-463. (PMID: 32152506) Nat Commun. 2021 Aug 25;12(1):5110. (PMID: 34433824) Science. 2016 Feb 12;351(6274):711-4. (PMID: 26912858) Curr Diab Rep. 2011 Dec;11(6):533-42. (PMID: 21912932) Diabetes. 2019 Sep;68(9):1830-1840. (PMID: 31175101) Diabetes Care. 2008 Aug;31(8):1546-9. (PMID: 18487476) Front Immunol. 2021 May 25;12:668680. (PMID: 34113344) Clin Exp Immunol. 2019 Dec;198(3):306-313. (PMID: 31132145) Diabetes. 2008 Apr;57(4):1084-92. (PMID: 18252895) |
| معلومات مُعتمدة: | R01 AI146202 United States AI NIAID NIH HHS; R01 DK081166 United States DK NIDDK NIH HHS; R21 AI133059 United States AI NIAID NIH HHS; R01 DK081166 United States DK NIDDK NIH HHS |
| المشرفين على المادة: | 0 (Insulin) 9035-68-1 (Proinsulin) 0 (C-Peptide) 0 (Chromogranin A) 0 (Peptides) 0 (Insulin, Regular, Human) 0 (Epitopes) 0 (Peptide Fragments) |
| تواريخ الأحداث: | Date Created: 20240131 Date Completed: 20240422 Latest Revision: 20240427 |
| رمز التحديث: | 20240427 |
| مُعرف محوري في PubMed: | PMC11043060 |
| DOI: | 10.2337/db23-0622 |
| PMID: | 38295386 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
|---|---|
| DOI: | 10.2337/db23-0622 |