Figure 4.

ER stress induces neo-antigen formation in β cells. (A) During normal conditions, proteins are translated and properly folded in the ER lumen. (B) During ER stress, proper protein folding is inhibited and misfolded proteins accumulate. (C) Ca²⁺ is released from the ER, significantly increasing the concentration of cytosolic Ca²⁺. (D) Heightened Ca²⁺ in the cytosol increases the activity of PTM enzymes, such as Tgase2 and PAD. (E) Activated Tgase2 and PAD modify β cell proteins, generating neo-antigens for the autoimmune response in T1D.