Fully competent dendritic cells as inducers of T cell anergy in autoimmunity

Mature immunologically competent dendritic cells are the most efficient ant igen-presenting cells that powerfully activate T cells and initiate and sus tain immune responses. Indeed, dendritic cells are able to efficiently capt ure antigens. express high levels of costimulatory molecules, and produce t he combination of cytokines required to create a powerful immune response. They are also considered to be important in initiating autoimmune disease b y efficiently presenting autoantigens to self-reactive T cells that, in thi s case, will mount a pathogenic autoimmune reaction. Triggering T cells is not a simple on-off procedure, as T cell receptor responds to minor changes in ligand with gradations of T cell activation and effector functions. The se "misfit" peptides have been called Altered Peptide Ligands, and have bee n shown to have important biological significance. Here, we show that fully capable dendritic cells may present. upon natural antigen processing, a se lf-epitope with Altered Peptide Ligands features that can unexpectedly indu ce anergy in a human autoreactive T cell clone. These results indicate that presentation of a self-epitope by immunologically competent dendritic cell s does not always mean "danger" and show a mechanism involved in the fine b alance between activation and tolerance induction in humans.