Dealing with Unwanted immunogenicity: the design and development of tolerogenic T cell epitopes

The regulation of immune responses to self and foreign antigens is vitally important to limit immune pathology associated with both infections and hypersensitivity conditions. Control of autoimmune and allergic conditions can be reinforced by tolerance induction with peptide epitopes; as yet, however, the mechanism is not understood. Peptides must mimic naturally processed epitopes Repetitive administration of soluble peptide induces peripheral tolerance in models of autoimmune disease and allergy. This is characterised by the generation of anergic, IL-10 secreting CD4+ T-cells with regulatory function. CD4+ T-cells become anergic following their first encounter with peptide. The loss of proliferative capacity correlates with a cytokine switch from a pro-inflammatory to a phenotype characterised by secretion of the anti-inflammatory cytokine IL-10. IL-10 Treg cells suppress dendritic cell maturation, prevent Th1 cell differentiation and thereby create a negative feedback loop for Th1 driven immune pathology. These findings demonstrate that Th1 responses can be self-limiting in the context of peripheral tolerance to a self-antigen. Similar findings relating to Th2 mediated immune responses will be discussed.