Fine peptide specificity of cytotoxic T lymphocytes directed against adenovirus-induced tumours and peptide-MHC binding.
A peptide encoded by the adenovirus type 5 early region I (Ad5 EI) is the target structure for H-2Db-restricted cytotoxic T lymphocytes (CTL) that are capable of tumour eradication in vivo. With the use of a set of peptides in which each individual amino acid (aa) was deleted out of the sequence, we analyzed to what extent these deletion mutant peptides were still recognized by an Ad5-specific CTL clone and which deletion mutant peptides still bound to major histocompatibility-complex (MHC) class-I molecules. Binding was analyzed with RMA-S cells that express largely empty and unstable MHC-class-I molecules which are stabilized by peptide binding. We show here that flanking an 8 mer aa sequence, originally described by us as the minimal epitope recognized by CTL, 2 additional aa are important for MHC binding. This leads to the conclusion that this 10-mer peptide is optimal for MHC binding and T-cell recognition. Areas of the peptide primarily involved in binding to MHC or in T-cell recognition are delineated.
Kast
W M
WM
Department of Immunohaematology, Academic Hospital, Leiden, The Netherlands.
Melief
C J
CJ
D000260:Adenoviruses, Human / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D003602:Cytotoxicity, Immunologic; D004622:Embryo, Mammalian; D006183:H-2 Antigens / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides