Type 1 diabetes (T1D) may be linked to insulin-related peptides that mistakenly bond to other peptides within the pancreas and spleen, a new study suggests. These findings may help explain the mystery of why the immune system attacks insulin-producing cells in people with T1D. Recently some evidence has begun to explore the role that peptides, short chains of amino acids that cells use to carry out various processes, may play. Thomas Delong et al. had previously identified an antigen and a related peptide, WE14, that trigger an autoimmune response to insulin-producing β cells in mice with T1D. Yet WE14 alone could not explain the autoimmune response seen in T1D. This led to team to hypothesize whether a combination of peptides that are covalently bonded, called hybrid insulin peptides (HIPs), may be triggering the response. They created two libraries of peptides and cross-referenced them, identifying a number of culprit peptides that link with WE14 and that are found significantly more frequently in the pancreas of mice, the organ where insulin is produced. Furthermore, these hybrid peptides were much more easily recognized by the T cells than the individual peptides. The researchers then explored whether human T cells recognize these HIPs. Analysis of samples donated by two T1D patients revealed that a number of their T cells specifically targeted these HIPs. Therefore the authors suggest that HIPs play a central role in the pathogenesis of T1D by prompting the immune system to attack insulin-producing β cells.