التفاصيل البيبلوغرافية
| العنوان: |
Proinsulin C-peptide is an autoantigen in people with type 1 diabetes. |
| المؤلفون: |
So, Michelle, Elso, Colleen M., Tresoldi, Eleonora, Pakusch, Miha, Pathiraja, Vimukthi, Wentworth, John M., Harrison, Leonard C., Krishnamurthy, Balasubramanian, Thomas, Helen E., Rodda, Christine, Cameron, Fergus J., McMahon, Jacinta, Kay, Thomas W. H., Mannering, Stuart I. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 10/16/2018, Vol. 115 Issue 42, p10732-10737, 6p |
| مصطلحات موضوعية: |
C-peptide, AUTOANTIGENS, TYPE 1 diabetes, T cells, EPITOPES, IMMUNOTHERAPY |
| مستخلص: |
Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells, found within the islets of Langerhans in the pancreas, are destroyed by islet-infiltrating T cells. Identifying the antigenic targets of beta-cell reactive T cells is critical to gain insight into the pathogenesis of T1D and develop antigen-specific immunotherapies. Several lines of evidence indicate that insulin is an important target of T cells in T1D. Because many human islet-infiltrating CD4+ T cells recognize C-peptide-derived epitopes, we hypothesized that full-length C-peptide (PI33-63), the peptide excised from proinsulin as it is converted to insulin, is a target of CD4+ T cells in people with T1D. CD4+ T cell responses to full-length C-peptide were detected in the blood of: 14 of 23 (>60%) people with recent-onset T1D, 2 of 15 (>13%) people with long-standing T1D, and 1 of 13 (<8%) HLA-matched people without T1D. C-peptide-specific CD4+ T cell clones, isolated from six people with T1D, recognized epitopes from the entire 31 amino acids of C-peptide. Eighty-six percent (19 of 22) of the C-peptide-specific clones were restricted by HLA-DQ8, HLA-DQ2, HLA-DQ8trans, or HLA-DQ2trans, HLA alleles strongly associated with risk of T1D. We also found that full-length C-peptide was a much more potent agonist of some CD4+ T cell clones than an 18mer peptide encompassing the cognate epitope. Collectively, our findings indicate that proinsulin C-peptide is a key target of autoreactive CD4+ T cells in T1D. Hence, full-length C-peptide is a promising candidate for antigen-specific immunotherapy in T1D. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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