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  • Title: Identification of a novel HLA-A*0201-restricted, cytotoxic T lymphocyte epitope in a human glioma-associated antigen, interleukin 13 receptor alpha2 chain.
    Author: Okano F, Storkus WJ, Chambers WH, Pollack IF, Okada H.
    Journal: Clin Cancer Res; 2002 Sep; 8(9):2851-5. PubMed ID: 12231526.
    Abstract:
    PURPOSE: Interleukin 13 receptor alpha2-chain (IL-13Ralpha2) has been reported to be abundantly and specifically overexpressed in glioblastoma multiforme. Here we report the identification of a CTL epitope derived from the IL-13Ralpha2. EXPERIMENTAL DESIGN: Mature dendritic cells (DCs) were pulsed with each of the synthetic peptides that were designed, based on a binding affinity-based prediction and a proteosomal cleavage site prediction system, and used to stimulate autologous CD8+ T cells from an HLA-A2+ healthy donor. After four to six cycles of restimulation, the immunoreactivity of the T cells was analyzed for specific IFN-gamma production and CTL reactivity. RESULTS: Of the five peptides tested, IL-13Ralpha(345-354) (WLPFGFILI) induced a CD8(+) T-cell line that specifically produced IFN-gamma in response to HLA-A2+ T2 cells pulsed with the relevant peptide and lysed these cells. Peptide titration assays demonstrated that half-maximal lysis of IL-13Ralpha(345-354) peptide-reactive CD8(+) T cells required peptide loading concentration of approximately 5 nM. Perhaps most importantly, this CD8(+) T-cell line also displayed lytic activity against the HLA-A2+ human glioma cell lines that express IL-13Ralpha2. CONCLUSIONS: This novel CTL epitope may therefore serve as an attractive component of peptide-based vaccines to treat glioma and as a surrogate marker of T-cell immune responses in patients before and after therapy.
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