Antigen-specific immunomodulation via altered peptide ligands

An important subgroup of human cellular receptors uses peptides as signaling molecules. Modifications of these signaling peptides, usually by amino acid substitutions in crucial receptor contact sites (i.e., altered peptide ligands, APLs), is an approach for highly selective and specific modulation of the receptor function. One of the major applications of APLs is immunology, where APLs have been examined for therapeutic modulation of T cell function, both for diseases characterized by unwanted activation of T cells (e.g., autoimmune diseases) and for disorders with suboptimal T cell activation (e.g., immunotherapy of cancers and infectious disorders). APLs also occur in vivo, for example, as escape mutants of infectious agents, and play an important role in thymic positive selection. We summarize current knowledge of the basic mechanisms of the effects of APLs with special focus on T cell receptor signaling and the use of APLs for the treatment of autoimmune diseases.