Epitopes described in "Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability."

Article Authors:S H van der Burg; M J Visseren; R M Brandt; W M Kast; C J Melief
Article Title:Immunogenicity of peptides bound to MHC class I molecules depends on the MHC-peptide complex stability.
Reference Detail
Reference ID:1003506
Abstract: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.
Affiliations:Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Reference Type:Literature
PubMed ID:8617954
Journal:J Immunol
Journal Volume:156
Article Pages:3308-14
Journal ISSN:0022-1767
Article Chemical List:Epitopes;Gene Products, pol;HLA-A Antigens;Histocompatibility Antigens Class I
Article MeSH List:Amino Acid Sequence; Animals; Epitopes(chemistry; immunology ); Gene Products, pol(chemistry; immunology ); HIV(chemistry; immunology ); HLA-A Antigens(chemistry; genetics; immunology ); Hepatitis B virus(chemistry; immunology ); Histocompatibility Antigens Class I(chemistry; genetics; immunology ); Humans; Kinetics; Mice; Mice, Transgenic; Molecular Sequence Data; Papillomaviridae(chemistry; immunology ); Protein Binding(immunology ); T-Lymphocytes, Cytotoxic(chemistry; immunology )
Curation Last Updated:2015-12-10 20:01:46