Rapid peptide turnover and inefficient presentation of exogenous antigen critically limit the activation of self-reactive CTL by dendritic cells

This study evaluated to what extent presentation of exogenously acquired se lf-Ags via MBC class I molecules on DC might contribute to the activation o f self-reactive CTL and subsequent development of autoimmune disease. We sh ow here by using the rat insulin promotor lymphocytic choriomeningitis viru s glycoprotein model of autoimmune diabetes that the activation of self-rea ctive CTL by DC after uptake of exogenous Ag is very limited, first by the short half-life of MHC class I-associated peptides on DC in vitro and in vi vo, and second by the rather inefficient MHC class I presentation of cell-a ssociated self-Ags by DC, These two mechanisms are probably crucial in esta blishing high thresholds for the induction of self-reactive CTL that preven t autoimmune sequelae after release of sequestered and previously immunolog ically ignored tissue Ags.