Journal article

Proinsulin C-peptide is an autoantigen in people with type 1 diabetes

Michelle So, Colleen M Elso, Eleonora Tresoldi, Miha Pakusch, Vimukthi Pathiraja, John M Wentworth, Leonard C Harrison, Balasubramanian Krishnamurthy, Helen E Thomas, Christine Rodda, Fergus J Cameron, Jacinta McMahon, Thomas WH Kay, Stuart I Mannering

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2018

Abstract

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...

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Grants

Awarded by Juvenile Diabetes Research Foundation


Awarded by National Health and Medical Research Council


Awarded by Diabetes Australia Research Trust Millennium Award


Awarded by NHMRC


Funding Acknowledgements

We thank Prof. Vijaya Sundararajan for statistical advice. We thank Erin Hill, Gowri Selvaraj, Elham Mohammed-Nur, and Ashvin Nursing for clinical assistance. This work was supported by Juvenile Diabetes Research Foundation Grant 5-CDA-2014-210-A-N (to S.I.M.), National Health and Medical Research Council Grant GNT123586 (to S.I.M.), Diabetes Australia Research Trust Millennium Award Y17M1-MANS (to S.I.M.), and the Operational Infrastructure Support Program of the Victorian Government (S.I.M., H.E.T., and T.W.H.K.). M.S. is supported by NHMRC Postgraduate Scholarship APP1094337 and JDRF PhD Top-up Scholarship.