Proteasome-catalysed peptide splicing in Type 1 Diabetes

Proteasome is the main producer of the epitopes presented on MHC-I molecules to the CD8⁺ T cells. The epitopes could be produced by peptide-bond hydrolysis or by proteasome-catalysed peptide splicing (PCPS). Proteasome-generated antigenic spliced peptides seem to be much more frequent than expected. Therefore, they can extend the antigenic landscape of cells to a grey area where self and non-self could be misjudged by the immune system. Do we have enough information to reckon if PCPS plays a relevant role in autoimmunity? Can the investigation of PCPS lead to the discovery of new autoantigens in the contest of T1D? Is there any relation between the Hybrid Insulin Peptides discovered by DeLong and colleagues, and presented onto MHC-II complexes, and proteasome-generated spliced peptides, which are presented by MHC-I complexes?