PMID- 8617954 OWN - NLM STAT- MEDLINE DCOM- 19960613 LR - 20210103 IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 156 IP - 9 DP - 1996 May 1 TI - Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability. PG - 3308-14 AB - The impact of the MHC class I peptide binding stability on the immunogenicity of particular peptide Ags in class I-restricted cytotoxic T lymphocyte responses is not clearly established. Therefore, we have determined the dissociation rate of each peptide from MHC class I at 37 degrees C and compared this to that of a consensus CTL epitope. Newly defined immunogenic peptides formed relatively stable MHC-peptide complexes as shown by their low dissociation rates, whereas nonimmunogenic peptides displayed high dissociation rates. In addition virtually all previously described HLA-A*0201-restricted T cell epitopes showed low dissociation rates. Furthermore, we show that the immunogenicity of HIV-1-derived peptides can be predicted more accurately by their dissociation rate than by the MHC class I binding affinity. Selection of peptides based on affinity and their dissociation rate leads to a more precise 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 processing rules, therefore have important implications for the selection of peptides in peptide-based vaccines. FAU - van der Burg, S H AU - van der Burg SH AD - Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands. FAU - Visseren, M J AU - Visseren MJ FAU - Brandt, R M AU - Brandt RM FAU - Kast, W M AU - Kast WM FAU - Melief, C J AU - Melief CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Epitopes) RN - 0 (Gene Products, pol) RN - 0 (HLA-A Antigens) RN - 0 (Histocompatibility Antigens Class I) SB - IM MH - Amino Acid Sequence MH - Animals MH - Epitopes/*chemistry/*immunology MH - Gene Products, pol/chemistry/immunology MH - HIV/chemistry/immunology MH - HLA-A Antigens/*chemistry/genetics/*immunology MH - Hepatitis B virus/chemistry/immunology MH - Histocompatibility Antigens Class I/*chemistry/genetics/*immunology MH - Humans MH - Kinetics MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Papillomaviridae/chemistry/immunology MH - Protein Binding/immunology MH - T-Lymphocytes, Cytotoxic/chemistry/immunology EDAT- 1996/05/01 00:00 MHDA- 1996/05/01 00:01 CRDT- 1996/05/01 00:00 PHST- 1996/05/01 00:00 [pubmed] PHST- 1996/05/01 00:01 [medline] PHST- 1996/05/01 00:00 [entrez] PST - ppublish SO - J Immunol. 1996 May 1;156(9):3308-14.