Prioritization of infectious epitopes for translational investigation in type 1 diabetes etiology

Molecular mimicry is one mechanism by which infectious agents are thought to trigger islet autoimmunity in type 1 diabetes. With a growing number of reported infectious agents and islet antigens, strategies to prioritize the study of infectious agents are critically needed to expedite translational research into the etiology of type 1 diabetes. In this work, we developed an in-silico pipeline for assessing molecular mimicry in type 1 diabetes etiology based on sequence homology, empirical binding affinity to specific MHC molecules, and empirical potential for T-cell immunogenicity. We then assess whether potential molecular mimics were conserved across other pathogens known to infect humans. Overall, we identified 61 potentially high-impact molecular mimics showing sequence homology, strong empirical binding affinity, and empirical immunogenicity linked with specific MHC molecules. We further found that peptide sequences from 32 of these potential molecular mimics were conserved across several human pathogens. These findings facilitate translational evaluation of molecular mimicry in type 1 diabetes etiology by providing a curated and prioritized list of peptides from infectious agents for etiopathologic investigation. These results may also provide evidence for generation of infectious and HLA-specific preclinical models and inform future screening and preventative efforts in genetically susceptible populations. [Display omitted] •This work assesses molecular mimicry in type 1 diabetes using computational methods•We empirically evaluate sequence homology, binding affinity, and immunogenicity•This method identified 61 potential molecular mimics in type 1 diabetes etiology•32 potential molecular mimics were conserved across other human pathogens•This pipeline can be adapted to investigate mimicry in other autoimmune diseases