Figure 4.

Simplified model of β-cell damage leading to antigen presentation. T cells can directly kill β cells through a cytotoxic process, but they can also influence β-cell destruction via release of mediators such as cytokines, chemokines, or perforin. Cytokine activation of inducible nitric oxide synthase can activate ER stress response signaling (Oyadomari et al. 2001)—pathways collectively known as the unfolded protein response (UPR). It is therefore conceivable that cell stress including UPR may be a potential contributor to β-cell toxicity in T1D. Processing of autoantigens within β cells generates peptides that are then taken up by antigen-presenting cells (APCs), either as whole dead β cells or β-cell fragments, for eventual further processing/presentation of these islet peptides to self-reactive T cells.