Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses

K. Tajima, A. Demachi, Y. Ito, K. Nishida, Yoshiki Akatsuka, K. Tsujimura, H. Kuwano, T. Mitsudomi, T. Takahashi, K. Kuzushima

Research output: Contribution to journalArticle

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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-γ 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.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalTissue Antigens
Volume64
Issue number6
DOIs
Publication statusPublished - 01-12-2004

Fingerprint

T-cells
Cell Adhesion Molecules
Cytotoxic T-Lymphocytes
HLA Antigens
Epitopes
Peptides
Assays
Enzyme-Linked Immunospot Assay
Major Histocompatibility Complex
Clone Cells
Cells
Epithelial Cells
Epithelial Cell Adhesion Molecule
Carcinoma
T-Lymphocytes
Cell Line
Enzymes
Ethnic Groups
Immunotherapy
Dendritic Cells

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Genetics

Cite this

Tajima, K. ; Demachi, A. ; Ito, Y. ; Nishida, K. ; Akatsuka, Yoshiki ; Tsujimura, K. ; Kuwano, H. ; Mitsudomi, T. ; Takahashi, T. ; Kuzushima, K. / Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses. In: Tissue Antigens. 2004 ; Vol. 64, No. 6. pp. 650-659.
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Tajima, K, Demachi, A, Ito, Y, Nishida, K, Akatsuka, Y, Tsujimura, K, Kuwano, H, Mitsudomi, T, Takahashi, T & Kuzushima, K 2004, 'Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses', Tissue Antigens, vol. 64, no. 6, pp. 650-659. https://doi.org/10.1111/j.1399-0039.2004.00329.x

Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses. / Tajima, K.; Demachi, A.; Ito, Y.; Nishida, K.; Akatsuka, Yoshiki; Tsujimura, K.; Kuwano, H.; Mitsudomi, T.; Takahashi, T.; Kuzushima, K.

In: Tissue Antigens, Vol. 64, No. 6, 01.12.2004, p. 650-659.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of an epitope from the epithelial cell adhesion molecule eliciting HLA-A*2402-restricted cytotoxic T-lymphocyte responses

AU - Tajima, K.

AU - Demachi, A.

AU - Ito, Y.

AU - Nishida, K.

AU - Akatsuka, Yoshiki

AU - Tsujimura, K.

AU - Kuwano, H.

AU - Mitsudomi, T.

AU - Takahashi, T.

AU - Kuzushima, K.

PY - 2004/12/1

Y1 - 2004/12/1

N2 - 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-γ 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.

AB - 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-γ 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.

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