Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles
Identifieur interne : 004932 ( Main/Exploration ); précédent : 004931; suivant : 004933Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles
Auteurs : Esteban Celis [États-Unis] ; John Fikes [États-Unis] ; Peggy Wentworth [États-Unis] ; John Sidney [États-Unis] ; Scott Southwood [États-Unis] ; Ajesh Maewal [États-Unis] ; Marie-France Del Guercio [États-Unis] ; Alessandro Sette [États-Unis] ; Brian Livingston [États-Unis]Source :
- Molecular Immunology [ 0161-5890 ] ; 1994.
English descriptors
- Teeft :
- Accession number, Affinity, Allele, Amino, Amino acid residues, Amino acid sequence, Amino acids, Antigen processing, Assay, Base insertion, Binder, Binding affinity, Binding assays, Binding capacity, Binding motifs, Binding peptides, Bruggen, Caucasian population, Celis, Cell line, Cell lines, Coding region, Cytotoxic, Epitope, Gene product, Genetic analysis, Genomic, Good affinity, High affinity, Immun, Intermediate affinity, Kast, Kubo, Lymphocyte, Mage, Malignant melanoma, Melanoma, Melanoma patient, Melanoma patients, Melanoma tumors, Molecule, Motif, Motif type, Normal individuals, Normal tissues, Octyl glucoside, Open reading frame, Original sequence, Peptide, Peptide binding, Peptide sequences, Peptides binding, Positive melanoma cell line, Potential antigenic peptides, Present study, Ruppert, Sequence analysis, Sette, Specific motifs, Standard peptides, Such peptides, Synthetic peptides, Systematic analysis, Transgenic mice, Tumor antigen, Tumor antigens.
Abstract
Abstract: Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ⩽ 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.
Url:
DOI: 10.1016/0161-5890(94)90158-9
Affiliations:
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Le document en format XML
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<term>Amino acid residues</term>
<term>Amino acid sequence</term>
<term>Amino acids</term>
<term>Antigen processing</term>
<term>Assay</term>
<term>Base insertion</term>
<term>Binder</term>
<term>Binding affinity</term>
<term>Binding assays</term>
<term>Binding capacity</term>
<term>Binding motifs</term>
<term>Binding peptides</term>
<term>Bruggen</term>
<term>Caucasian population</term>
<term>Celis</term>
<term>Cell line</term>
<term>Cell lines</term>
<term>Coding region</term>
<term>Cytotoxic</term>
<term>Epitope</term>
<term>Gene product</term>
<term>Genetic analysis</term>
<term>Genomic</term>
<term>Good affinity</term>
<term>High affinity</term>
<term>Immun</term>
<term>Intermediate affinity</term>
<term>Kast</term>
<term>Kubo</term>
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<term>Melanoma patients</term>
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<term>Motif type</term>
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<term>Normal tissues</term>
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<term>Open reading frame</term>
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<term>Peptide</term>
<term>Peptide binding</term>
<term>Peptide sequences</term>
<term>Peptides binding</term>
<term>Positive melanoma cell line</term>
<term>Potential antigenic peptides</term>
<term>Present study</term>
<term>Ruppert</term>
<term>Sequence analysis</term>
<term>Sette</term>
<term>Specific motifs</term>
<term>Standard peptides</term>
<term>Such peptides</term>
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<front><div type="abstract" xml:lang="en">Abstract: Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ⩽ 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.</div>
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