An HLA-A11-specific motif in nonamer peptides derived from viral and cellular proteins.
T lymphocytes recognize their antigenic targets as peptides associated with major histocompatibility complex molecules. The HLA-A11 allele, a preferred restriction element for Epstein-Barr virus (EBV)-specific cytotoxic T-lymphocyte responses, presents an immunodominant epitope derived from the EBV nuclear antigen 4. Subpicomolar concentrations of a synthetic nonamer peptide, IVTDFSVIK, corresponding to amino acids 416-424 of the EBV nuclear antigen 4 sequence, can sensitize phytohemagglutinin-stimulated blasts to lysis by EBV-specific HLA-A11-restricted cytotoxic T-lymphocytes. We show that micromolar concentrations of this peptide induce assembly and surface expression of HLA-A11 in an A11-transfected subline of the peptide transporter mutant cell line T2. Using the IVTDFSVIK peptide and a series of synthetic nonamer peptides, differing from the original sequence by single amino acid substitutions, we have defined a motif for HLA-A11-binding peptides. This predicts the presence of a hydrophobic amino acid in position 2, amino acids with small side chains in positions 3 and 6, and a lysine in position 9. Using this motif, we have identified a peptide in the carboxyl-terminal end of wild-type p53, ELNEALELK, which is able to induce HLA-A11 assembly as efficiently as the IVTDFSVIK viral peptide.
Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden.
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Zhang
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Gavioli
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Klein
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Masucci
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000956:Antigens, Viral / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens; D005455:Fluorescent Antibody Technique; D015234:HLA-A Antigens / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D059870:HLA-A11 Antigen; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007525:Isoelectric Focusing; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000276:immunology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D010446:Peptide Fragments; D001613:beta 2-Microglobulin; D008715:Methionine