Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen.
OBJECTIVE
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 alpha2 receptor (IL-13Ralpha2) 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-13Ralpha2 as a target antigen of malignant glioma cells, and then identified a potential HLA-A24-restricted peptide derived from IL-13Ralpha2.


METHODS
The expression of IL-13Ralpha2 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-13Ralpha2 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-13Ralpha2. Of the 5 peptides tested, P174 (WYEGLDHAL) was found to be the most useful for the induction of HLA-A24-restricted and IL-13Ralpha2-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-13Ralpha2 and HLA-A24.


CONCLUSIONS
Interleukin-13Ralpha2 is a glioma-specific antigen, and the immunogenic peptide P174 may contribute to a peptide-based immunotherapy against malignant glioma cells expressing HLA-A24.
Shimato
Shinji
S
Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
Natsume
Atsushi
A
Wakabayashi
Toshihiko
T
Tsujimura
Kunio
K
Nakahara
Norimoto
N
Ishii
Jun
J
Ito
Motokazu
M
Akatsuka
Yoshiki
Y
Kuzushima
Kiyotaka
K
Yoshida
Jun
J
D000951:Antigens, Neoplasm / Q000378:metabolism*; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000502:physiology*; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000502:physiology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D053663:Interleukin-13 Receptor alpha2 Subunit