The good, the bad and the ugly: how altered peptide ligands modulate immunity

Background: The basis of T cell immune responses is the specific recognition of an immunogenic peptide epitope by a T cell receptor. Peptide alterations of such T cell epitopes with single or few amino acid variations can have drastic effects on the outcome of this recognition. These altered peptide ligands can act as modulators of immune responses as they are capable of downregulating or upregulating responses. Objective/methods: We review how altered peptide ligands can have ‘good’ ‘bad’ and ‘ugly’ outcomes in treating diseases. Results/conclusion: Altered peptide ligands have been used as immunotherapeutics in autoimmune (and allergic) diseases, infectious diseases and cancer. In the next five years we anticipate seeing a number of altered peptide ligands in clinical trials, progressing from contradictory classifications of good, bad or ugly, to the exciting outcome of ‘useful’.