A Novel Tolerogenic Antibody Targeting Disulfide-Modified Autoantigen Effectively Prevents Type 1 Diabetes in NOD Mice.

ABSTRACT: Increasing evidence suggested that the islet amyloid polypeptide (IAPP) is an essential autoantigen in the pathogenesis of type 1 diabetes (T1D) in humans and non-obese diabetic (NOD) mice. A unique disulfide containing IAPP-derived peptide KS20 is one of the highly diabetogenic peptides in NOD mice. The KS20-reactive T cells, including prototypic pathogenic BDC5.2.9, accumulate in the pancreas of prediabetic and diabetic mice and contribute to disease development. We generated a monoclonal antibody (LD96.24) that interacts with IA^g7-KS20 complexes with high affinity and specificity. LD96.24 recognized the IA^g7-KS20 disulfide loop and blocked the interaction between IA^g7-KS20 tetramers and cognate T cells but not other autoantigen-reactive T cells. The i

SUBMITTER: Li W 

PROVIDER: S-EPMC9406144 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature