Zachary Shaheen ^1,2,3* Alexander J. Dwyer ^2,3,4 Brian T. Fife ^2,3,4

• ¹ Pediatric Rheumatology, Allergy, & Immunology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, United States
• ² Center for Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States
• ³ Center for Autoimmune Disease Research, Department of Medicine, Medical School, University of Minnesota, Minneapolis, Minnesota, United States
• ⁴ Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School, Minneapolis, United States

Autoimmune diabetes is a disease characterized by the selective destruction of insulin-secreting β-cells of the endocrine pancreas by islet-reactive T cells. Autoimmune disease requires a complex interplay between host genetic factors and environmental triggers that promote the activation of such antigen-specific T lymphocyte responses. Given the critical involvement of self-reactive T lymphocyte in diabetes pathogenesis, understanding how these T lymphocyte populations contribute to disease is essential to develop targeted therapeutics. To this end, several key antigenic T lymphocyte epitopes have been identified and studied to understand their contributions to disease with the aim of developing effective treatment approaches for translation to the clinical setting. In this review, we discuss the role of pathogenic islet-specific T lymphocyte responses in autoimmune diabetes, the mechanisms and cell types governing autoantigen presentation, and therapeutic strategies targeting such T lymphocyte responses for the amelioration of disease.