Analysis of human CD4+ T cell responses to hybrid peptide epitopes implicated in type 1 diabetes

Type 1 diabetes (T1D) develops when insulin-producing -cells within pancreatic islets are destroyed by the host’s immune system. How autoreactive T cells recognise hybrid insulin peptides (HIPs) presented by HLA-DQ8 is unknown. We demonstrated the CD4+ T cells extracted from the peripheral blood of recent-onset and pancreas of deceased T1D patients were responded to HLA-DQ8 presenting HIPs. Our structural findings provided insights into the details of how these CD4+ T cells recognized naturally occurring antigen (C-peptide) and cross-reacted to HIPs.