Type 1 Diabetes Mellitus as a Potential Immune Response to Virally Stressed Beta Cells: A Beta-Cell-First Hypothesis of Antigen Modification and Immune Recognition

Viral infection, secretory stress, disturbed proinsulin folding, and post-translational modification could alter beta-cell antigens and increase their presentation to T cells. Supporting observations include enterovirus-associated changes in beta-cell stress pathways, viral markers and HLA class I hyperexpression in pancreatic tissue, and experimental recognition of stress-associated modified antigens by diabetogenic T cells. These findings support a beta-cell-first contribution to pathogenesis, but do not establish that all beta-cell elimination is beneficial or confined to infected cells.