Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles

Esteban Celis, John Fikes, Peggy Wentworth, John Sidney, Scott Southwood, Ajesh Maewal, Marie France Del Guercio, Alessandro Sette, Brian Livingston

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59 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1423-1430
Number of pages8
JournalMolecular Immunology
Volume31
Issue number18
DOIs
StatePublished - Dec 1994
Externally publishedYes

Keywords

  • MAGE-1
  • cytotoxic T lymphocytes
  • peptide-HLA interactions
  • tumor antigen

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

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    Celis, E., Fikes, J., Wentworth, P., Sidney, J., Southwood, S., Maewal, A., Del Guercio, M. F., Sette, A., & Livingston, B. (1994). Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles. Molecular Immunology, 31(18), 1423-1430. https://doi.org/10.1016/0161-5890(94)90158-9