The symposium, Diverse Antigens Targeted in Type 1 Diabetes, on Saturday, June 21, from 8:00–9:30 a.m., in Room W196 BC of the McCormick Place Convention Center, will spotlight the different molecules and pathways that drive autoimmune responses in type 1 diabetes.

“Type 1 diabetes is a complex disease that affects over 1.5 million people in the United States,” said Emrah Altindis, PhD, Assistant Professor of Biology at Boston College and Adjunct Faculty Member at Harvard Medical School and the Joslin Diabetes Center. “Although we have known about type 1 diabetes since ancient times, the cause of the disease remains unknown to date. To prevent type 1 disease, there is an urgent and unmet need to understand the underlying cause, especially the triggers of the autoimmune response that drive type 1 diabetes development.”
The symposium will focus on different antigen targets involved in potentiating and sustaining autoimmunity in type 1 diabetes, such as B cells, autoantibody sources that also serve as antigen-presenting cells, and CD4-positive T cells, which can be reactive to native or hybrid epitopes, Dr. Altindis explained. He will talk about gut microbiome-associated and -derived peptide epitopes that are molecular mimics of native epitopes.
“Immune regulation by the gut microbiome is where microbial peptides may intersect with autoimmunity,” he said. “There are at least 1,000 species in our gut microbiome, accounting for over a kilogram of bacteria. This is a vast reservoir of microbial proteins, some with structural similarity with native protein epitopes, and may act as antigen mimics, stimulating aberrant autoimmune responses.”
Development of autoantibodies, targeting “self” antigens, is an early and critical step in type 1 diabetes pathogenesis. Dr. Altindis and colleagues have identified many microbial molecular mimics of autoantigens, including insulin-specific epitopes. Of these T cells specific to insulin, B chain 9–23 epitope (insB:9–23) was detected in the pancreas and in circulation in patients with type 1 diabetes. Exposure of nonobese diabetic (NOD) mouse models to insB:9–23 epitope potentiates autoimmunity, leading to development of type 1 diabetes.
Researchers identified a peptide from the gut commensal bacteria, Parabacteroides distasonis (P. distasonis), that acts as a molecular mimic of insB:9–23, activating an insB:9–23-specific T-cell response.
“We showed a two-fold increase in diabetes onset in NOD mice colonized with this commensal bacterium, but not other species,” he said.
In a proof-of-concept study, Dr. Altindis and colleagues translated these findings in human children by analyzing data from the longitudinal DIABIMMUNE study that focused on the gut microbiome in subjects from Russia, Finland, and Estonia.
“Our analyses showed that the presence of the P. distasonis insB:9–23-like peptide increased the risk of seroconversion, i.e., risk of developing autoantibodies, by several-fold,” Dr. Altindis said. “We also showed that exposure to this microbial peptide impacts the immune cell composition in the pancreas.”
Autoimmune diseases are increasing in prevalence globally, Dr. Altindis noted, adding that more mechanistic hypothesis-driven studies are needed to assess the effects of the gut microbiome in causing, delaying, and/or preventing autoimmune pathogenesis, as well as to untangle the true causal drivers.
The session will feature three additional presentations. Maki Nakayama, MD, PhD, Professor of Pediatrics at the University of Colorado Anschutz Medical Campus, will talk about identification and tracking of antigen reactivity. Brian T. Fife, PhD, Professor of Medicine at the University of Minnesota, will cover the fates of CD4 T cells reactive to native or hybrid epitopes. Mia Smith, PhD, DVM, Assistant Professor at the University of Colorado Anschutz Medical Campus, will explore self-reactive B cells.
On-demand access to recorded presentations will be available to registered participants following the conclusion of the 85th Scientific Sessions, from June 25–August 25.

Watch the Scientific Sessions On-Demand after the Meeting
Extend your learning on the latest advances in diabetes research, prevention, and care after the 85th Scientific Sessions conclude. From June 25–August 25, registered participants will have on-demand access to presentations recorded in Chicago via the meeting website.