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Hybrid insulin peptides are neo-epitopes for CD4 T cells in autoimmune diabetes

Baker, Rocky L.*; Jamison, Braxton L.*; Haskins, Kathryn

Current Opinion in Endocrinology, Diabetes and Obesity: August 2019 - Volume 26 - Issue 4 - p 195–200
doi: 10.1097/MED.0000000000000490
DIABETES AND ENDOCHRINE PANCREAS II: Edited by Peter A. Gottlieb
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Purpose of review The current review covers recent advances in our knowledge of the newest autoantigen neo-epitopes in type 1 diabetes (T1D): hybrid insulin peptides or HIPs. These ligands for autoreactive T cells are formed by peptide fusion, a novel posttranslational modification process that we first reported in 2016.

Recent findings Two major HIPs in the nonobese diabetic mouse model, ligands for diabetogenic CD4 T-cell clones, have been incorporated into tetramers and used to track HIP-reactive T cells during progression of disease. HIPs have also been used in strategies for induction of antigen-specific tolerance and show promise for delaying or reversing disease in the nonobese diabetic mouse. Importantly, CD4 T cells reactive to various HIPs have been detected in the islets and peripheral blood mononuclear cell of T1D patients and newly developed human T-cell clones are being employed to gather more data on the phenotype and function of HIP-reactive T cells in patients.

Summary These new hybrid insulin peptide epitopes may provide the basis for establishing autoreactive T cells as biomarkers of disease and as potential tolerogens for treatment of T1D.

Department of Immunology and Microbiology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA

Correspondence to Kathryn Haskins, Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA. Tel: +1 720 900 8650; e-mail: Katie.haskins@ucdenver.edu

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