TY - JOUR
T1 - Unique features in the presentation of insulin epitopes in autoimmune diabetes
T2 - an update
AU - Wan, Xiaoxiao
AU - Unanue, Emil R.
N1 - Funding Information:
We thank members of the Unanue laboratory who contributed to our findings discussed here. In particular, we highlight Javier Carrero, Stephen Ferris, James Mohan and Boris Calderon. We also thank Dr. James W. Thomas for his major contribution to our studies cited in Reference [52•]. Our work is supported by research grants from National Institutes of Health (DK058177 and AI114551) and the Juvenile Diabetes Research Foundation (SRA 293 and 512).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-Ag7 class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets. Therefore, a better understanding of insulin presentation is crucial for assessing disease pathogenesis and therapeutic intervention. Here, we summarize recent advances in insulin presentation events that underlie the essential role of this autoantigen in driving autoimmune diabetes.
AB - Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-Ag7 class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets. Therefore, a better understanding of insulin presentation is crucial for assessing disease pathogenesis and therapeutic intervention. Here, we summarize recent advances in insulin presentation events that underlie the essential role of this autoantigen in driving autoimmune diabetes.
UR - http://www.scopus.com/inward/record.url?scp=85018791645&partnerID=8YFLogxK
U2 - 10.1016/j.coi.2017.04.001
DO - 10.1016/j.coi.2017.04.001
M3 - Review article
C2 - 28456018
AN - SCOPUS:85018791645
SN - 0952-7915
VL - 46
SP - 30
EP - 37
JO - Current Opinion in Immunology
JF - Current Opinion in Immunology
ER -