ALTERED PEPTIDE LIGAND DESIGN - ALTERING IMMUNE-RESPONSES TO CLASS-I MHC PEPTIDE COMPLEXES/

Class I proteins are responsible for binding proteins from endogenousl y synthesized proteins and displaying them on the cell surface. Our un derstanding of this process has reached the point where we can manipul ate the biochemical properties of peptide/class I binding and determin e the effects of this alteration on subsequent immune responses. In th is article, we will review the biochemistry of peptide/class I binding , and the effects of structure on this interaction between class I pro teins and their peptide ligands. We will review the data which suggest that the major relevant biochemical parameter of class I peptide bind ing is the off-rate. We will show that the design of altered ligands w ith improved binding, thermostability and immunogenicity is possible.