Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity.

ABSTRACT: A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-A^g7 even in the absence of DM, and this property is related to the type 1 diabetes-associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-A^g7 These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. Rapid C

SUBMITTER: Ito Y 

PROVIDER: S-EPMC6170167 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature