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

Research output: Contribution to journalArticle

59 Citations (Scopus)

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 - Jan 1 1994
Externally publishedYes

Fingerprint

HLA-A Antigens
Neoplasm Antigens
Epitopes
Alleles
Peptides
HLA-A1 Antigen
HLA-A11 Antigen
HLA-A24 Antigen
Neoplasms
Immunotherapy
Sequence Analysis
Melanoma
Vaccines
Genes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Cite this

Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles. / Celis, Esteban; Fikes, John; Wentworth, Peggy; Sidney, John; Southwood, Scott; Maewal, Ajesh; Del Guercio, Marie France; Sette, Alessandro; Livingston, Brian.

In: Molecular Immunology, Vol. 31, No. 18, 01.01.1994, p. 1423-1430.

Research output: Contribution to journalArticle

Celis, E, Fikes, J, Wentworth, P, Sidney, J, Southwood, S, Maewal, A, Del Guercio, MF, Sette, A & Livingston, B 1994, 'Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles', Molecular Immunology, vol. 31, no. 18, pp. 1423-1430. https://doi.org/10.1016/0161-5890(94)90158-9
Celis, Esteban ; Fikes, John ; Wentworth, Peggy ; Sidney, John ; Southwood, Scott ; Maewal, Ajesh ; Del Guercio, Marie France ; Sette, Alessandro ; Livingston, Brian. / Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles. In: Molecular Immunology. 1994 ; Vol. 31, No. 18. pp. 1423-1430.
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