IDENTIFICATION OF POTENTIAL CTL EPITOPES OF TUMOR-ASSOCIATED ANTIGEN MAGE-1 FOR 5 COMMON HLA-A ALLELES

被引:62
作者
CELIS, E
FIKES, J
WENTWORTH, P
SIDNEY, J
SOUTHWOOD, S
MAEWAL, A
DELGUERCIO, MF
SETTE, A
LIVINGSTON, B
机构
[1] Cytel Corporation, San Diego, CA 92121
关键词
TUMOR ANTIGEN; CYTOTOXIC T LYMPHOCYTES; MAGE-1; PEPTIDE HLA INTERACTIONS;
D O I
10.1016/0161-5890(94)90158-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (K-d less than or equal to 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.
引用
收藏
页码:1423 / 1430
页数:8
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