IMMUNOGENICITY OF PEPTIDES BOUND TO MHC CLASS-I MOLECULES DEPENDS ON THE MHC-PEPTIDE COMPLEX STABILITY

The impact of the MHC class I peptide binding stability on the immunog enicity of particular peptide Ags in class I-restricted cytotoxic T ly mphocyte responses is not clearly established, Therefore, we have dete rmined the dissociation rate of each peptide from MHC class I at 37 de grees C and compared this to that of a consensus CTL epitope, Newly de fined immunogenic peptides formed relatively stable MHC-peptide comple xes as shown by their low dissociation rates, whereas nonimmunogenic p eptides displayed high dissociation rates, In addition virtually all p reviously described HLA-A0201 -restricted T cell epitopes showed low dissociation rates, Furthermore, we show that the immunogenicity of HI V-1-derived peptides can be predicted more accurately by their dissoci ation rate than by the MHC class I binding affinity, Selection of pept ides based on affinity and their dissociation rate leads to a more pre cise identification of candidate CTL epitopes than selection based on affinity alone. These results help to understand why some peptides are recognized by CTL and, along with detailed knowledge of protein proce ssing rules, therefore have important implications for the selection o f peptides in peptide-based vaccines.