Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen: Laboratory investigation

Shinji Shimato, Atsushi Natsume, Toshihiko Wakabayashi, Kunio Tsujimura, Norimoto Nakahara, Jun Ishii, Motokazu Ito, Yoshiki Akatsuka, Kiyotaka Kuzushima, Jun Yoshida

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Object. The human leukocyte antigen-A24 (HLA-A24) allele is highly expressed in Asians. This allele is expressed in 60% of the Japanese population and in a significant number of people of other ethnicities. The interleukin-13 type α2 receptor (IL-13Rα2) has been shown to be a glioma-specific antigen, and is abundantly expressed in a majority of high-grade astrocytomas. In this study, the authors first investigated the suitability of IL-13Rα2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Rα2. Methods. The expression of IL-13Rα2 in glioma tissues was examined by reverse transcription- polymerase chain reaction analysis. To identify the desired epitope, the authors selected 5 candidate peptides from IL-13Rα2 that were predicted to bind to HLA-A24. The lytic activity of cytotoxic T lymphocytes (CTLs) induced by peptide-pulsed dendritic cells was analyzed against various glioma cell lines and freshly isolated human glioma cells. Results. In a series of glioma tissues obtained in 29 patients, the authors found that > 50% of high-grade gliomas expressed IL-13Rα2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Rα2-specific CTLs. A CTL line induced by P174 also showed antigen-specific cytotoxicity to surgically removed glioma cells depending on their level of expression of IL-13Rα2 and HLA-A24. Conclusions. Interleukin-13Rα2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.

Original languageEnglish
Pages (from-to)117-122
Number of pages6
JournalJournal of Neurosurgery
Volume109
Issue number1
DOIs
Publication statusPublished - 01-07-2008
Externally publishedYes

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Interleukin-13 Receptors
T-Lymphocyte Epitopes
HLA Antigens
Glioma
Antigens
Peptides
Cytotoxic T-Lymphocytes
Alleles
Interleukin-2 Receptors
Interleukins
Astrocytoma
Immunotherapy
Dendritic Cells
Reverse Transcription
Epitopes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology

Cite this

Shimato, Shinji ; Natsume, Atsushi ; Wakabayashi, Toshihiko ; Tsujimura, Kunio ; Nakahara, Norimoto ; Ishii, Jun ; Ito, Motokazu ; Akatsuka, Yoshiki ; Kuzushima, Kiyotaka ; Yoshida, Jun. / Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen : Laboratory investigation. In: Journal of Neurosurgery. 2008 ; Vol. 109, No. 1. pp. 117-122.
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title = "Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen: Laboratory investigation",
abstract = "Object. The human leukocyte antigen-A24 (HLA-A24) allele is highly expressed in Asians. This allele is expressed in 60{\%} of the Japanese population and in a significant number of people of other ethnicities. The interleukin-13 type α2 receptor (IL-13Rα2) has been shown to be a glioma-specific antigen, and is abundantly expressed in a majority of high-grade astrocytomas. In this study, the authors first investigated the suitability of IL-13Rα2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Rα2. Methods. The expression of IL-13Rα2 in glioma tissues was examined by reverse transcription- polymerase chain reaction analysis. To identify the desired epitope, the authors selected 5 candidate peptides from IL-13Rα2 that were predicted to bind to HLA-A24. The lytic activity of cytotoxic T lymphocytes (CTLs) induced by peptide-pulsed dendritic cells was analyzed against various glioma cell lines and freshly isolated human glioma cells. Results. In a series of glioma tissues obtained in 29 patients, the authors found that > 50{\%} of high-grade gliomas expressed IL-13Rα2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Rα2-specific CTLs. A CTL line induced by P174 also showed antigen-specific cytotoxicity to surgically removed glioma cells depending on their level of expression of IL-13Rα2 and HLA-A24. Conclusions. Interleukin-13Rα2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.",
author = "Shinji Shimato and Atsushi Natsume and Toshihiko Wakabayashi and Kunio Tsujimura and Norimoto Nakahara and Jun Ishii and Motokazu Ito and Yoshiki Akatsuka and Kiyotaka Kuzushima and Jun Yoshida",
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Shimato, S, Natsume, A, Wakabayashi, T, Tsujimura, K, Nakahara, N, Ishii, J, Ito, M, Akatsuka, Y, Kuzushima, K & Yoshida, J 2008, 'Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen: Laboratory investigation', Journal of Neurosurgery, vol. 109, no. 1, pp. 117-122. https://doi.org/10.3171/JNS/2008/109/7/0117

Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen : Laboratory investigation. / Shimato, Shinji; Natsume, Atsushi; Wakabayashi, Toshihiko; Tsujimura, Kunio; Nakahara, Norimoto; Ishii, Jun; Ito, Motokazu; Akatsuka, Yoshiki; Kuzushima, Kiyotaka; Yoshida, Jun.

In: Journal of Neurosurgery, Vol. 109, No. 1, 01.07.2008, p. 117-122.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor α2 chain, a glioma-associated antigen

T2 - Laboratory investigation

AU - Shimato, Shinji

AU - Natsume, Atsushi

AU - Wakabayashi, Toshihiko

AU - Tsujimura, Kunio

AU - Nakahara, Norimoto

AU - Ishii, Jun

AU - Ito, Motokazu

AU - Akatsuka, Yoshiki

AU - Kuzushima, Kiyotaka

AU - Yoshida, Jun

PY - 2008/7/1

Y1 - 2008/7/1

N2 - Object. The human leukocyte antigen-A24 (HLA-A24) allele is highly expressed in Asians. This allele is expressed in 60% of the Japanese population and in a significant number of people of other ethnicities. The interleukin-13 type α2 receptor (IL-13Rα2) has been shown to be a glioma-specific antigen, and is abundantly expressed in a majority of high-grade astrocytomas. In this study, the authors first investigated the suitability of IL-13Rα2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Rα2. Methods. The expression of IL-13Rα2 in glioma tissues was examined by reverse transcription- polymerase chain reaction analysis. To identify the desired epitope, the authors selected 5 candidate peptides from IL-13Rα2 that were predicted to bind to HLA-A24. The lytic activity of cytotoxic T lymphocytes (CTLs) induced by peptide-pulsed dendritic cells was analyzed against various glioma cell lines and freshly isolated human glioma cells. Results. In a series of glioma tissues obtained in 29 patients, the authors found that > 50% of high-grade gliomas expressed IL-13Rα2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Rα2-specific CTLs. A CTL line induced by P174 also showed antigen-specific cytotoxicity to surgically removed glioma cells depending on their level of expression of IL-13Rα2 and HLA-A24. Conclusions. Interleukin-13Rα2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.

AB - Object. The human leukocyte antigen-A24 (HLA-A24) allele is highly expressed in Asians. This allele is expressed in 60% of the Japanese population and in a significant number of people of other ethnicities. The interleukin-13 type α2 receptor (IL-13Rα2) has been shown to be a glioma-specific antigen, and is abundantly expressed in a majority of high-grade astrocytomas. In this study, the authors first investigated the suitability of IL-13Rα2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Rα2. Methods. The expression of IL-13Rα2 in glioma tissues was examined by reverse transcription- polymerase chain reaction analysis. To identify the desired epitope, the authors selected 5 candidate peptides from IL-13Rα2 that were predicted to bind to HLA-A24. The lytic activity of cytotoxic T lymphocytes (CTLs) induced by peptide-pulsed dendritic cells was analyzed against various glioma cell lines and freshly isolated human glioma cells. Results. In a series of glioma tissues obtained in 29 patients, the authors found that > 50% of high-grade gliomas expressed IL-13Rα2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Rα2-specific CTLs. A CTL line induced by P174 also showed antigen-specific cytotoxicity to surgically removed glioma cells depending on their level of expression of IL-13Rα2 and HLA-A24. Conclusions. Interleukin-13Rα2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.

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