Islet Autoantigens: Structure, Function, Localization, and Regulation

被引：70

作者：

Arvan, Peter ^{[1
]}

Pietropaolo, Massimo ^{[1
]}

Ostrov, David ^{[2
]}

Rhodes, Christopher J. ^{[3
]}

机构：

[1] Univ Michigan, Sch Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48105 USA

[2] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA

[3] Univ Chicago, Dept Med, Kovler Diabet Ctr, Chicago, IL 60637 USA

来源：

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE | 2012年 / 2卷 / 08期

关键词：

PANCREATIC BETA-CELLS; GLUTAMIC-ACID DECARBOXYLASE; ZINC TRANSPORTER ZNT8; ENDOPLASMIC-RETICULUM STRESS; NONOBESE DIABETIC MICE; RESTRICTED T-CELLS; CLASS-III ALLELES; INSULIN-SECRETION; PROINSULIN BIOSYNTHESIS; TRANSLATIONAL CONTROL;

D O I：

10.1101/cshperspect.a007658

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Islet autoantigens associated with autoimmune type 1 diabetes (T1D) are expressed in pancreatic beta cells, although many show wider patterns of expression in the neuroendocrine system. Within pancreatic beta cells, every T1D autoantigen is in one way or another linked to the secretory pathway. Together, these autoantigens play diverse roles in glucose regulation, metabolism of biogenic amines, as well as the regulation, formation, and packaging of secretory granules. The mechanism(s) by which immune tolerance to islet-cell antigens is lost during the development of T1D, remains unclear. Antigenic peptide creation for immune presentation may potentially link to the secretory biology of beta cells in a number of ways, including proteasomal digestion of misfolded products, exocytosis and endocytosis of cell-surface products, or antigen release from dying beta cells during normal or pathological turnover. In this context, we evaluate the biochemical nature and immunogenicity of the major autoantigens in T1D including (pro)insulin, GAD65, ZnT8, IA2, and ICA69.

引用

页数：20

共 198 条

[21] Sequence Variation in Promoter of Ica1 Gene, Which Encodes Protein Implicated in Type 1 Diabetes, Causes Transcription Factor Autoimmune Regulator (AIRE) to Increase Its Binding and Down-regulate Expression [J].