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) |