C-terminal modification of the insulin B:11-23 peptide creates superagonists in mouse and human type 1 diabetes.

ABSTRACT: A polymorphism at β57 in some major histocompatibility complex class II (MHCII) alleles of rodents and humans is associated with a high risk for developing type 1 diabetes (T1D). However, a highly diabetogenic insulin B chain epitope within the B:9-23 peptide is presented poorly by these alleles to a variety of mouse and human CD4 T cells isolated from either nonobese diabetic (NOD) mice or humans with T1D. We have shown for both species that mutations at the C-terminal end of this epitope dramatically improve presentation to these T cells. Here we present the crystal structures of these mutated peptides bound to mouse IA^g7 and human HLA-DQ8 that show how the mutations function to improve T-cell activation. In both peptide binding grooves, the mutation of B:22R to E in the pepti

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5776820 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature