Lysosomal cathepsin creates chimeric epitopes for diabetogenic CD4 T cells via transpeptidation.

ABSTRACT: The identification of the peptide epitopes presented by major histocompatibility complex class II (MHCII) molecules that drive the CD4 T cell component of autoimmune diseases has presented a formidable challenge over several decades. In type 1 diabetes (T1D), recent insight into this problem has come from the realization that several of the important epitopes are not directly processed from a protein source, but rather pieced together by fusion of different peptide fragments of secretory granule proteins to create new chimeric epitopes. We have proposed that this fusion is performed by a reverse proteolysis reaction called transpeptidation, occurring during the catabolic turnover of pancreatic proteins when secretory granules fuse with lysosomes (crinophagy). Here, we demonstrate several h

SUBMITTER: Reed B 

PROVIDER: S-EPMC7590512 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature