Recognition of pancreatic beta cell antigens by autoreactive T lymphocytes plays a central role in the pathogenesis of insulin-dependent type 1 diabetes. Recent results suggest that non-conventional antigenic epitope processing and presentation may contribute to triggering and maintaining autoreactive responses. Moreover, promising results raise hope that autoantigens may become safe and specific therapeutics for type 1 diabetes in the future.

In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control antigen processing and presentation. Here, we show that in response to lipopolysaccharides, protein synthesis is rapidly enhanced in DCs. This enhancement occurs via a PI3K-dependent signaling pathway and is key for DC activation. In addition, we show that later on, in a manner similar to viral or apoptotic stress, DC activation leads to the phosphorylation and proteolysis of important translation initiation factors, thus inhibiting cap-dependent translation. This inhibition correlates with major changes in the origin of the peptides presented by MHC class I and the ability of mature DCs to prevent cell death. Our observations have important implications in linking translation regulation with DC function and survival during the immune response.