MHC ligands as potential therapeutics in the treatment of autoimmune and allergic diseases

Inappropriate T-cell-mediated response is associated with a number of immunopathologies such as autoimmunity and allergy. T-cell activation requires recognition by T-cell receptors (TCRs), of complexes formed between molecules encoded by the major histocompatibility complex (MHC), and peptide antigens. Hence, approaches aimed at interfering with the formation of this ternary complex could potentially be useful in preventing or treating immunological disorders. Specific down-regulation or modulation of the immune response with peptide antigens or peptide antigen analogues has been demonstrated in various animal models. The use of antigenic peptides for tolerance induction, or high-affinity ligands that compete with autoantigenic epitopes for binding to MHC molecules, represent promising approaches in the development of new therapeutic agents with improved potency and, more importantly, reduced side-effects. Recent studies have also demonstrated that engagement of the TCR by an altered peptide ligand could lead to T-cell antagonism or partial activation. The therapeutic implications for antigen-specific modulation of the immune response will be covered in this review.