Identification of a SART-1-derived peptide capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes

✍ Scribed by Megumi Kikuchi; Masanobu Nakao; Yoshiko Inoue; Kazuko Matsunaga; Shigeki Shichijo; Hideaki Yamana; Kyogo Itoh

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 126 KB
• Volume: 81
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990505)81:3<459::aid-ijc21>3.0.co;2-6

✦ Synopsis

We have described the SART-1 gene-encoding peptides recognized by HLA-A2601-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). We now have investigated whether SART-1 encodes peptides capable of inducing the HLA-A24-restricted CTLs. Among the 18 different peptides with HLA-A24-binding motifs, the SART-1 690-698 peptide (EY-RGFTQDF) was most strongly recognized by the HLA-A24restricted and tumor-specific CTLs established from an esophageal cancer patient. After a third stimulation in vitro, this peptide induced HLA-A24-restricted CTLs recognizing the SART-1 259 ؉ tumor cells in PBMCs of all HLA-A24 homozygous and the majority of HLA-A24 heterozygous cancer patients and healthy donors tested. A similar activity, induction of CTLs from PBMCs, was observed in the Saccharomyces cerevisiae-derived nonapeptide (EYRGFTPMF) that shares 7 amino acids with the SART-1 690-698 peptide. The SART-1 690-698 peptide-induced CTL activity was significantly higher in PBMCs of HLA-A24 homozygotes than in HLA-A24 heterozygotes. The CTL precursor frequency in PBMCs after a third stimulation in vitro with the SART-1 690-698 peptide was high (G1/200) in both cancer patients and healthy donors. The SART-1 690-698 peptide could thus be useful for specific immunotherapy of HLA-A24 ϩ cancer patients.