Identification of a human leukocyte antigen-A24-restricted T-cell epitope derived from interleukin-13 receptor alpha2 chain, a glioma-associated antigen.

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 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.

journal_name

J Neurosurg

journal_title

Journal of neurosurgery

authors

Shimato S,Natsume A,Wakabayashi T,Tsujimura K,Nakahara N,Ishii J,Ito M,Akatsuka Y,Kuzushima K,Yoshida J

doi

10.3171/JNS/2008/109/7/0117

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

117-22

issue

1

eissn

0022-3085

issn

1933-0693

journal_volume

109

pub_type

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