title: T cell epitopes and post-translationally modified epitopes in type 1 diabetes.
abstract: Type 1 diabetes (T1D) is an autoimmune disease in which progressive loss of self-tolerance, evidenced by accumulation of auto-antibodies and auto-reactive T cells that recognize diverse self-proteins, leads to immune-mediated destruction of pancreatic beta cells and loss of insulin secretion. In this review, we discuss antigens and epitopes in T1D and the role that post-translational modifications play in circumventing tolerance mechanisms and increasing antigenic diversity. Emerging data suggest that, analogous to other autoimmune diseases such as rheumatoid arthritis and celiac disease, enzymatically modified epitopes are preferentially recognized in T1D. Modifying enzymes such as peptidyl deiminases and tissue transglutaminase are activated in response to beta cell stress, providing a mechanistic link between post-translational modification and interactions with the environment. Although studies of such responses in the at-risk population have been limited, current data suggests that breakdown in tolerance through post-translational modification represents an important checkpoint in the development of T1D.
authors.affiliation: Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA, USA. jmcginity@benaroyaresearch.org.
authors.forename: John W
authors.initials: JW
authors.lastname: McGinty
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, USA. mem212@pitt.edu.
authors.forename: Meghan L
authors.initials: ML
authors.lastname: Marré
authors.affiliation: Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA, USA. VBajzik@benaroyaresearch.org.
authors.forename: Veronique
authors.initials: V
authors.lastname: Bajzik
authors.affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA, USA. jdp51@pitt.edu.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Piganelli
authors.affiliation: Benaroya Research Institute at Virginia Mason, 1201 9th Ave, Seattle, WA, USA. ejames@benaroyaresearch.org.
authors.forename: Eddie A
authors.initials: EA
authors.lastname: James
mesh_terms: D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D011499:Protein Processing, Post-Translational; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
keywords: Autoimmune; HLA; Modified epitope; Post-translational; T cell; Type 1 diabetes