RRC ID 1336
著者 Tajima K, Demachi A, Ito Y, Nishida K, Akatsuka Y, Tsujimura K, Kuwano H, Mitsudomi T, Takahashi T, Kuzushima K.
タイトル Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses.
ジャーナル Tissue Antigens
Abstract Because the epithelial cell adhesion molecule (Ep-CAM) is expressed in almost all carcinomas and human leucocyte antigen (HLA)-A*2402 is the most common allele in many ethnic groups, including Japanese, the identification of peptide sequences, which elicit HLA-A*2402-restricted Ep-CAM-specific cytotoxic T-lymphocyte (CTL) responses, would facilitate specific immunotherapy for various histological types of carcinomas. An epitope was identified through the following steps: (i) computer-based epitope prediction from the amino acid sequence of Ep-CAM, (ii) major histocompatibility complex (MHC) stabilization assay to determine the affinity of the predicted peptide with HLA-A*2402 molecules, (iii) stimulation of CD8+ T cells with peptide-pulsed dendritic cells and (iv) testing the CTL specificity by means of enzyme-linked immunospot (ELISPOT) assays, CTL assays and MHC/peptide-tetramer staining. Peripheral CD8+ T cells of four of five healthy donors after three rounds of stimulation with the peptide Ep-CAM173-181 (RYQLDPKFI) secreted interferon-gamma in ELISPOT assays when exposed to the peptide. A CTL clone specific to the peptide efficiently lysed Ep-CAM-expressing cancer cell lines in an HLA-A*2402-restricted fashion. Endogenous processing and presentation of the peptide in a lung cancer cell line were confirmed by means of cold target inhibition assays. The CTL clone was also lytic to normal bronchial epithelial cells but to a lesser extent at low effector: target ratios. All these data suggest that the peptide-specific CTL responses may play some roles both in anti-cancer and autoimmune reactions. The peptide should prove useful to study anti-Ep-CAM CTL responses among population possessing HLA-A*2402.
巻・号 64(6)
ページ 650-9
公開日 2004-12-1
DOI 10.1111/j.1399-0039.2004.00329.x
PII TAN329
PMID 15546337
MeSH Biomarkers, Tumor / immunology CD8-Positive T-Lymphocytes / immunology* Cell Adhesion Colonic Neoplasms / immunology Colonic Neoplasms / metabolism Colonic Neoplasms / pathology Dendritic Cells Epithelial Cells / immunology* Epitopes / immunology* HLA-A Antigens / immunology* HLA-A24 Antigen Humans Interferon-gamma / metabolism Lung Neoplasms / immunology* Lung Neoplasms / metabolism Lung Neoplasms / pathology Peptide Fragments / immunology Stomach Neoplasms / immunology Stomach Neoplasms / metabolism Stomach Neoplasms / pathology T-Lymphocytes, Cytotoxic / immunology* Tumor Cells, Cultured
IF 1.348
引用数 10
WOS 分野 PATHOLOGY IMMUNOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 LC-1/sq(RCB0455)